Neurofilament light chain in a phase 2 clinical trial of ibudilast in progressive multiple sclerosis.

BACKGROUND: Sensitive and specific biomarkers for use in progressive multiple sclerosis (MS) have not been established. We investigate neurofilament light (NfL) as a treatment response biomarker in progressive MS. OBJECTIVE: To evaluate whether ibudilast 100 mg/day alters serum and cerebrospinal fluid (CSF) levels of NfL in progressive MS. METHODS: In a protocol-defined exploratory analysis from a 2-year, phase 2 clinical trial of ibudilast in progressive MS (NCT01982942), serum samples were collected from 239 subjects and a subset contributed CSF and assayed using single-molecule assay (SIMOA) immunoassay. A mixed model for repeated measurements yielded log(NfL) as the response variable. RESULTS: The geometric mean baseline serum NfL was 31.9 and 28.8 pg/mL in placebo and ibudilast groups, respectively. The geometric mean baseline CSF NfL was 1150.8 and 1290.3 pg/mL in placebo and ibudilast groups, respectively. Serum and CSF NfL correlations were r = 0.52 and r = 0.78 at weeks 48 and 96, respectively. Over 96 weeks, there was no between-group difference in NfL in either serum (p = 0.76) or CSF (p = 0.46). After controlling for factors that may affect NfL, no effect of ibudilast on NfL in either serum or CSF was observed. CONCLUSION: Ibudilast treatment was not associated with a change in either serum or CSF NfL.

Comparison of Burnout and Empathy Among Millennial and Generation X Residents and Fellows: Associations with Training Level and Race but Not Generation Affiliation.

OBJECTIVE: The authors examine the associations of generational affiliation on empathy and burnout in a sample of millennial (born between 1982 and 2000) and Generation X (born between 1965 and 1981) residents and fellows. METHODS: At a single large institution during the 2013-2014 academic year, residents and fellows were asked to complete the Jefferson Scale of Physician Empathy and Maslach Burnout Inventory (MBI). Responses were combined with GME database content. Multivariable regression analysis included generation affiliation, race, gender, and post-graduate year (PGY) as covariates. RESULTS: The study sample included 388 millennial (mean age = 29.3) and 200 Generation X trainees (mean age = 34.6), with the response rate being 96.5%. Groups were statistically different by gender (p < 0.001) and PGY level (p < 0.001). After adjustment for gender, race, and PGY level, no statistically significant differences were found between millennial and Generation X groups in mean scores of empathy or burnout. Empathy was associated with PGY level (p = 0.0008) and race (p < 0.0001), with decreased empathy in advanced training levels and increased empathy in Hispanic/Latino race. Burnout rate was associated with PGY level (p = 0.001) but not generational affiliation (p = 0.6). The MBI depersonalization subscale was associated with PGY level (p < 0.001) and race (p = 0.0034), with decreased depersonalization in advanced training levels and Hispanic/Latino race. The emotional exhaustion and personal accomplishment MBI subscales did not demonstrate any significant associations in the multivariable regression model. CONCLUSIONS: In a compared sample of millennial and Generation X residents and fellows, PGY level and Hispanic/Latino race (though not generation affiliation) were significantly associated with both empathy and MBI depersonalization subscale scores, while only PGY level was significantly associated with burnout rate. This study presents further evidence of de-escalating burnout and declining empathy over the course of medical residency.

Assessment and documentation of incontinence-associated dermatitis after implementation of a standardised instrument: a comparative study.

OBJECTIVE: In this study, clinical nurses' documentation of incontinence-associated dermatitis (IAD) were compared with wound expert documentation before and after implementing a valid, reliable severity index (SI) instrument. METHODS: A prospective, non-equivalent, two group comparative design within three hospital medical units. Pre- and post-implementation skin condition documentation were compared by clinician type, and post-implementation IADSI scores were assessed for agreement using standard and weighted Kappa. RESULTS: Of 89 patients (pre-, n=48 and post-, n=38), mean (standard deviation) age was 72.4±13.7 years and 57.3% had IAD. Mean IADSI score was 13.2 (standard deviation: 10.5; range: 0-52), reflecting pink intact skin. Post-implementation, skin documentation between clinicians was more likely to match, from 35.4 to 84.2%, p<0.001. Post-implementation, after controlling for age, gender and race, the odds ration (OR) of matched documentation between clinicians was 5.80 ([95% confidence interval: 1.8, 18.6], p=0.003) compared with pre-implementation. In the post-implementation period, standard Kappas for agreement in clinical nurse-wound expert documentation in the lower back/buttocks/upper thigh areas ranged from 0.82 to 1.0, reflecting very good agreement. Weighted kappas ranged from 0.76 to 1.0, also reflecting good to very good agreement. CONCLUSION: Implementation of an IADSI assessment instrument improved accuracy of IAD documentation.

Comparison of laparoscopic jejunostomy tube to percutaneous endoscopic gastrostomy tube with jejunal extension: long-term durability and nutritional outcomes.

INTRODUCTION: Enteral access through the jejunum is indicated when patients cannot tolerate oral intake or gastric feeding. While multiple approaches for feeding jejunal access exist, few studies have compared the efficacy of these techniques. The purpose of this study was to investigate the long-term durability, re-intervention rates, and nutritional outcomes following percutaneous endoscopic gastrostomy tubes with jejunal extension tubes (PEG-JET) versus laparoscopic jejunostomy tubes (j-tubes). METHODS: Retrospective chart review was performed on all patients who underwent PEG-JET or laparoscopic jejunostomy tube placement from January 2005 through December 2015 at our institution. Thirty-day and long-term outcomes were compared between the two groups. RESULTS: A total of 105 patients underwent PEG-JET and 307 patients underwent laparoscopic j-tube placement during the defined study period. In terms of 30-day outcomes, patients who underwent PEG-JET placement were significantly more likely to experience a tube dislodgement event (p = 0.005) and undergo a re-intervention (p < 0.001). Patients who had a laparoscopic j-tube placed were significantly more likely to meet their enteral feeding goals (p = 0.002) and less likely to require nutritional supplementation with total parenteral nutrition (TPN) (p < 0.001). With regard to long-term outcomes, patients who underwent PEG-JET placement were significantly more likely to experience tube occlusion (p < 0.001) and require an endoscopic or surgical tube re-intervention (p < 0.001). Patients who underwent laparoscopic j-tube placement were significantly more likely to experience a tube site leak (p = 0.015) but were less likely to require nutritional supplementation with TPN (p = 0.001). CONCLUSION: Laparoscopic jejunostomy tubes provide more durable long-term enteral access compared to PEG-JET. Consideration should be given to laparoscopic jejunostomy tube placement in eligible patients who cannot tolerate oral intake or gastric enteral feeding.

Validation of a Model for Predicting Pressure Injury Risk in Patients With Vascular Diseases.

PURPOSE: The purpose of this study was to validate a 10-factor model of risk factors for hospital-acquired pressure injury (HAPI) risk in patients with vascular disease. SUBJECTS AND SETTING: Medical reviews identified 800 patients from a 1063 admissions to a 1400 bed quarternary care hospital in the midwestern United States. DESIGN: Retrospective review of medical records. METHODS: Medical records of consecutive patients treated during an 18-month period on a medical-surgical vascular progressive care unit were reviewed. Ten previously identified risk factors for HAPI-(1) lower right ankle-brachial index, (2) low Braden Scale for Pressure Sore Risk score, (3) cared for in intensive care unit, (4) low serum hematocrit values, (4) elevated serum hematocrit levels (5) female gender, (6) nonwhite individual, (7) atherosclerosis, (8) diabetes mellitus, (9) elevated blood urea nitrogen levels, and (10) high body mass index-were compared to determine their ability to predict development of HAPI. Logistic regression model was used to validate the model. RESULTS: One hundred forty-six (16.1%) out of 800 patients developed an HAPI. The 10-factor risk model produced a concordance index of predicted to actual risk of 0.851, and the likelihood of developing an HAPI based on the model was significant (P < .001). CONCLUSIONS: A 10-factor model of HAPI risk was developed for patients with vascular disease. Routine assessment of risk factors is crucial in planning individualized interventions to diminish the risk of HAPI occurrences.

Communication Skills Training for Physicians Improves Patient Satisfaction.

BACKGROUND: Skilled physician communication is a key component of patient experience. Large-scale studies of exposure to communication skills training and its impact on patient satisfaction have not been conducted. OBJECTIVE: We aimed to examine the impact of experiential relationship-centered physician communication skills training on patient satisfaction and physician experience. DESIGN: This was an observational study. SETTING: The study was conducted at a large, multispecialty academic medical center. PARTICIPANTS: Participants included 1537 attending physicians who participated in, and 1951 physicians who did not participate in, communication skills training between 1 August 2013 and 30 April 2014. INTERVENTION: An 8-h block of interactive didactics, live or video skill demonstrations, and small group and large group skills practice sessions using a relationship-centered model. MAIN MEASURES: Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS), Clinician and Group Consumer Assessment of Healthcare Providers and Systems (CGCAHPS), Jefferson Scale of Empathy (JSE), Maslach Burnout Inventory (MBI), self-efficacy, and post course satisfaction. KEY RESULTS: Following the course, adjusted overall CGCAHPS scores for physician communication were higher for intervention physicians than for controls (92.09 vs. 91.09, p < 0.03). No significant interactions were noted between physician specialty or baseline CGCAHPS and improvement following the course. Significant improvement in the post-course HCAHPS Respect domain adjusted mean was seen in intervention versus control groups (91.08 vs. 88.79, p = 0.02) and smaller, non-statistically significant improvements were also seen for adjusted HCAHPS communication scores (83.95 vs. 82.73, p = 0.22). Physicians reported high course satisfaction and showed significant improvement in empathy (116.4 ± 12.7 vs. 124 ± 11.9, p < 0.001) and burnout, including all measures of emotional exhaustion, depersonalization, and personal accomplishment. Less depersonalization and greater personal accomplishment were sustained for at least 3 months. CONCLUSIONS: System-wide relationship-centered communication skills training improved patient satisfaction scores, improved physician empathy, self-efficacy, and reduced physician burnout. Further research is necessary to examine longer-term sustainability of such interventions.

Complex or monosomal karyotype and not blast percentage is associated with poor survival in acute myeloid leukemia and myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2): a Bone Marrow Pathology Group study.

Acute myeloid leukemia and myelodysplastic syndrome with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) have a poor prognosis. Indeed, the inv(3)(q21q26.2)/t(3;3)(q21;q26.2) has been recognized as a poor risk karyotype in the revised International Prognostic Scoring System. However, inv(3)(q21q26.2)/t(3;3)(q21;q26.2) is not among the cytogenetic abnormalities pathognomonic for diagnosis of acute myeloid leukemia irrespective of blast percentage in the 2008 WHO classification. This multicenter study evaluated the clinico-pathological features of acute myeloid leukemia/myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and applied the revised International Prognostic Scoring System to myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2). A total of 103 inv(3)(q21q26.2)/t(3;3)(q21;q26.2) patients were reviewed and had a median bone marrow blast count of 4% in myelodysplastic syndrome (n=40) and 52% in acute myeloid leukemia (n=63) (P<0.001). Ninety-one percent of patients showed characteristic dysmegakaryopoiesis. There was no difference in overall survival between acute myeloid leukemia and myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) (12.9 vs. 7.9 months; P=0.16). Eighty-three percent of patients died (median follow up 7.9 months). Complex karyotype, monosomal karyotype and dysgranulopoiesis (but not blast percentage) were independent poor prognostic factors in the entire cohort on multivariable analysis. The revised International Prognostic Scoring System better reflected overall survival of inv(3)(q21q26.2)/t(3;3)(q21;q26.2) than the International Prognostic Scoring System but did not fully reflect the generally dismal prognosis. Our data support consideration of myelodysplastic syndrome with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) as an acute myeloid leukemia with recurrent genetic abnormalities, irrespective of blast percentage.

Low 25-hydroxyvitamin D levels in people with a solid tumor cancer diagnosis: the tip of the iceberg?

PURPOSE: Low serum 25-hydroxyvitamin D [25(OH)D] levels have been linked to both cancer incidence and poor prognosis. The frequency of 25(OH)D tests and clinical factors associated with low levels in cancer patients are unknown. PATIENTS AND METHODS: Electronic medical records from 2006 to 2007 of 39,252 adult solid tumor patients were reviewed. Data included demographics, cancer sites (primary and metastatic), and first serum 25(OH)D level during the study period. Laboratory data, comorbidities, selected medications, and anticancer treatment within the prior 2 months were recorded. Data were compared between (1) those tested and not tested and (2) 25(OH)D levels≤10 ng/ml (deficient), 11-30 ng/ml (insufficient), and ≥31 ng/ml (sufficient). Stepwise logistic regression identified independent predictors of low serum 25(OH)D levels. RESULTS: The cohort was 86% Caucasian and 48% female with a mean age of 63±14 years (mean±SD). The most prevalent cancer was breast (19%). In total, 2,098 (5%) had a 25(OH)D test. Of those tested, 133 (6%) had levels≤10 ng/ml and 1,311 (62%) 11-30 ng/ml. Tests were more frequent in females and in those with breast, skin, and thyroid cancers (P<0.001). Low 25(OH)D levels were associated (in univariable analyses) with male gender, non-Caucasian race, gastrointestinal tumor primary sites, metastatic disease, benign liver disease, low serum albumin, and elevated liver enzymes. Significant factors in multivariable models for 25(OH)D levels≤10 and ≤30 ng/ml included non-Caucasian race, primary cancer site, and test calendar month. Vitamin D supplements and recent antineoplastic medication were associated with sufficient levels. CONCLUSIONS: Low (deficient or insufficient) 25(OH)D serum levels were highly prevalent in people with solid tumors. Vitamin D tests were infrequent and paradoxically less often done in high-risk groups. Tests were more frequent in females and in those with breast, skin, and thyroid cancers. Further research should examine role of routine 25(OH)D tests, the clinical consequences of low levels, and therapeutic supplementation in people with 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.

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.

A new survey to evaluate conflict of interest policies at academic medical centers.

BACKGROUND: A majority of academic medical centers (AMCs) have now adopted conflict of interest policies (COI) to address relationships with pharmaceutical and device industries that can increase the risk of bias in patient care, education and research. However, AMCs may have little information on the impact of their policies. This paper provides a new method, which is a free, publicly-available survey, to fill this information gap and improve COI programs at AMCs. METHODS & FINDINGS: The survey, piloted in three AMCs and designed in collaboration with national conflicts of interest policy experts, covers a range of universal compliance-related concerns, which allows institutions to tailor questions to align with their own policies and culture. The survey was low-burden, and provided important data for these AMCs to evaluate their policies. A descriptive analysis of the pooled pilot site data (n = 1578) was performed, which found that a majority of respondents did not have financial ties with industry and a majority was satisfied with specific COI policies at their institutions. The analysis also showed that the survey is sensitive to differences that AMCs will find meaningful. For instance, individuals with industry ties were significantly more likely than individuals without ties to think that COI policies unnecessarily hindered interactions with industry (p = .004), were ineffective at reducing harm to patients (p < .001), and were ineffective in reducing bias in medical education (p>.001). CONCLUSION: The survey is now free and publicly available for use by any institution. AMCs can use the results to update and refine policies, and to provide ongoing education regarding existing policies.

Risk of overall mortality and cardiovascular events in patients with type 2 diabetes on dual drug therapy including metformin: A large database study from the Cleveland Clinic.

BACKGROUND: The aim of the present study was to assess the risk of overall mortality, coronary artery disease (CAD), and congestive heart failure (CHF) in patients with type 2 diabetes mellitus (T2DM) treated with metformin (MF) and an additional antidiabetic agent. METHODS: A retrospective cohort study was conducted using an academic health center enterprise-wide electronic health record (EHR) system to identify 13,185 adult patients (>18 years) with T2DM from January 2008 to June 2013 and received a prescription for MF in combination with a sulfonylurea (SU; n = 9419), thiazolidinedione (TZD; n = 1846), dipeptidyl peptidase-4 inhibitor (DPP-4i; n = 1487), or a glucagon-like peptide-1 receptor agonist (GLP-1a; n = 433). Multivariate Cox models with propensity analysis were used to compare cohorts, with MF+SU serving as the comparator group. RESULTS: The mean (±SD) age was 60.6 ± 12.6 years, with 54.6% male and 75.8% Caucasians. The median follow-up was 4 years. There were 1077 deaths, 1733 CAD events, and 528 CHF events in 55,100 person-years of follow-up. A higher risk of CHF was observed with MF+DPP-4i use (hazard ratio [HR] 1.104; 95% confidence interval [CI] 1.04-1.17; P = 0.001). A trend towards improved overall survival for users of MF+TZD (HR 0.86; 95% CI 0.74-1.0; P = 0.05) and MF+GLP-1a (HR 0.569; 95% CI 0.30-1.07; P = 0.08) was observed. No significant differences in the risk of CAD were identified. CONCLUSIONS: Consistent with recent studies, our results raise concern for an increased risk of CHF with use of DPP-4i.

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.

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.

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.

Postmenopausal hormone replacement and venous thromboembolism following hip and knee arthroplasty.

Hormone replacement therapy has been associated with venous thromboembolism. Controversy exists regarding the appropriate management of hormone replacement in the perioperative setting and in other situations--such as acute illness--predisposing to acute venous thromboembolism. We performed a case-control study to determine whether perioperative hormone replacement is associated with venous thromboembolism following hip and knee arthroplasty. 108 patients with postoperative venous thrombosis were matched by age, date and type of surgery, and surgeon with 210 controls without thrombosis. Perioperative hormone replacement use was no more prevalent in patients with postoperative thrombosis than those without. Eighteen (16.7%) women with post-operative thrombosis had taken perioperative hormone replacement compared to 49 (23.3%) of controls: odds ratio = 0.66; (95% CI 0.35-1.18; p=0.17). After multivariate analysis, the adjusted odds ratios were similar. Variables predicting post-operative thrombosis included: prior venous thromboembolism (OR = 2.3; p = 0.02), rheumatologic disease (OR = 2.2; p = 0.03), and absence of pharmacologic antithrombotic prophylaxis (OR = 13.4; p = 0.005). Cases and controls were otherwise similar. Users of hormone replacement were similar to non-users except that they were less likely to have coronary disease (OR 0.34; p = 0.03) or prior thrombosis (OR = 0.28; p = 0.04), and were younger (median age 67 versus 74 years; p <0.0001). We found no association between perioperative hormone replacement and post-operative thrombosis in patients undergoing major orthopaedic surgery. Routine discontinuation of these medications preoperatively--and possibly in other situations predisposing to thrombosis, such as acute medical illness--may be unnecessary in patients receiving appropriate pharmacologic antithrombotic prophylaxis.

Impact of nonmeasurable borders and variation in cross-section counts on intravascular ultrasound measurement of atherosclerotic plaque volume.

The inability to measure borders and variation in the number of 1-mm cross sections acquired from an identical length of vessel in serial intravascular ultrasound (IVUS) pullbacks represents potential errors in calculating volumes by IVUS. In a clinical IVUS trial, the percentage of nonmeasurable lumen and external elastic membrane borders, and the percent variation in the number of 1-mm cross sections acquired from an identical vessel length at 2 separate time points, were determined. A statistical model that simulated the effect of varying the percentage of the total number of cross sections in a pullback (i.e., sample fraction) was developed using SAS software. Mean and maximum errors for calculation of atheroma volume for each sample fraction were determined. The mean percentage of nonmeasurable lumen and external elastic membrane borders in an individual patient was 8.4 +/- 8.4% and 17.4 +/- 18.4%, respectively. Mean variation in the number of 1-mm cross sections acquired in serial studies was 5.6 +/- 6.2%. A decrease in sample fraction from 95% to 50% was associated with a linear increase in the mean and maximum errors in atheroma volume, from 2.0 +/- 0.9% and 5.9 +/- 3.0%, to 7.1 +/- 2.8% and 23.4 +/- 10.3%, respectively. Thus, nonmeasurable borders and variation in the number of 1-mm cross sections acquired from an identical length of vessel in serial studies are real considerations in clinical IVUS trials. However, given the reported incidence of these considerations in this clinical trial, our statistical model suggests that the impact of each of these considerations on atheroma volume calculation is small.

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.

High-frequency ultrasound in the measurement of pediatric craniofacial integrity.

OBJECTIVE: This study evaluates the use of high-frequency ultrasound in the measurement of the material nature of the pediatric craniofacial skeleton. STUDY DESIGN AND SETTING: Three desiccated human skulls, aged 1 year, 5 years, and adult, underwent ultrasonic evaluation at 6 sites on each hemicranium. RESULTS: The overall mean signal reflection coefficients for the infant, child, and adult skulls are 98.8 mV (13.75 mV SD), 172 mV (24.5 mV SD), and 230 mV (23.5 mV SD), respectively. The mean signal reflection coefficient is positively correlated with increasing chronological age. Comparison of intrasubject signal patterns suggests bone density fields, which vary as a function of growth. CONCLUSION: High-frequency ultrasound provides accurate measurements of the osseous impedance of the craniofacial skeleton. Pattern analysis suggests increases in skull density with greater growth and age. SIGNIFICANCE: Although further testing must be performed in vivo, high-frequency ultrasound may accurately measure the osseous impedance of the pediatric craniofacial skeleton. EBM RATING: C.

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.