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Objective:Infants with single ventricle physiology have arterial oxygen saturations between 75 and 85%. Home monitoring with daily pulse oximetry is associated with improved interstage survival. They are typically sent home with expensive, bulky, hospital-grade pulse oximeters. This study evaluates the accuracy of both the currently used Masimo LNCS and a relatively inexpensive, portable, and equipped with Bluetooth technology study device, by comparing with the gold standard co-oximeter.Design:Prospective, observational study.Setting:Single institution, paediatric cardiac critical care unit, and neonatal ICU.Interventions:none.Patients:Twenty-four infants under 12 months of age with baseline oxygen saturation less than 90% due to cyanotic CHD.Measurements and Results:Pulse oximetry with WristOx2 3150 with infant sensors 8008 J (study device) and Masimo LCNS saturation sensor connected to a Philips monitor (hospital device) were measured simultaneously and compared to arterial oxy-haemoglobin saturation measured by co-oximetry. Statistical analysis evaluated the performances of each and compared to co-oximetry with Schuirmann’s TOST equivalence tests, with equivalence defined as an absolute difference of 5% saturation or less. Neither the study nor the hospital device met the predefined standard for equivalence when compared with co-oximetry. The study device reading was on average 4.0% higher than the co-oximeter, failing to show statistical equivalence (p = 0.16). The hospital device was 7.4% higher than the co-oximeter and also did not meet the predefined standard for equivalence (p = 0.97).Conclusion:Both devices tended to overestimate oxygen saturation in this patient population when compared to the gold standard, co-oximetry. The study device is at least as accurate as the hospital device and offers the advantage of being more portable with Bluetooth technology that allows reliable, efficient data transmission. Currently FDA-approved, smaller portable pulse oximeters can be considered for use in home monitoring programmes.

Background There is inadequate power to perform a valid clinical trial in pediatric heart transplantation (HT) using a conventional end-point, because the disease is rare and hard end-points, such as death or graft loss, are infrequent. We sought to develop and validate a surrogate end-point involving the cumulative burden of post-transplant complications to predict death/graft loss to power a randomized clinical trial of maintenance immunosuppression in pediatric HT. Methods Pediatric Heart Transplant Study (PHTS) data were used to identify all children who underwent an isolated orthotopic HT between 2005 and 2014 who survived to 6 months post-HT. A time-varying Cox model was used to develop and evaluate a surrogate end-point comprised of 6 major adverse transplant events (MATEs) (acute cellular rejection [ACR], antibody-mediated rejection [AMR], infection, cardiac allograft vasculopathy [CAV], post-transplant lymphoproliferative disease [PTLD] and chronic kidney disease [CKD]) occurring between 6 and 36 months, where individual events were defined according to international guidelines. Two thirds of the study cohort was used for score development, and one third of the cohort was used to test the score. Results Among 2,118 children, 6.4% underwent graft loss between 6 and 36 months post-HT, whereas 39% developed CKD, 34% ACR, 34% infection, 9% AMR, 4% CAV and 2% PTLD. The best predictive score involved a simple MATE score sum, yielding a concordance probability estimate (CPE) statistic of 0.74. Whereas the power to detect non-inferiority (NI), assuming the NI hazard ratio of 1.45 in graft survival was 10% (assuming 200 subjects and 6% graft loss rate), the power to detect NI assuming a 2-point non-inferiority margin was >85% using the MATE score. Conclusion The MATE score reflects the cumulative burden of MATEs and has acceptable prediction characteristics for death/graft loss post-HT. The MATE score may be useful as a surrogate end-point to power a clinical trial in pediatric HT.

Background: Moderate weight loss and physical activity (PA) can prevent or delay type 2 diabetes however there is a need for innovative, effective programs to promote PA in high-risk individuals. Purpose: We examined the effect of a group-based adaption of the DPP lifestyle intervention implemented in partnership with the YMCA (YDPP) on changes in moderate-vigorous physical activity (MVPA) in economically disadvantaged adults with prediabetes. The effects of psychosocial and community-level factors were explored. Methods: Participants were randomly assigned to YDPP or brief counseling. Accelerometer data from 216 participants were used to identify: 1) change in MVPA and 2) sedentary behavior over 24 months. Results: YDPP had no significant effect on either outcome. Baseline PA and crime were associated with less MVPA while higher perceived health and green space were associated with more MVPA over time. Baseline sedentary behavior, perceived health, and green space were inversely related to being sedentar...

Objective To examine health care utilization among veterans with both chronic pain and posttraumatic stress symptoms. Methods Retrospective cohort study of 40,716 veterans in a VA regional network from January 1, 2002 to January 1, 2007. Veterans were categorized into pain-only, posttraumatic stress disorder symptoms (PTSD)-only, and pain plus PTSD (pain+PTSD) comparison groups. Negative binomial models were used to compare adjusted rates of primary care, mental health, and specialty pain service use, as well as opioids, benzodiazepines, nonopioid analgesics, and antidepressant prescriptions. Rates of clinic visits were calculated by days per year, and rates of medication use were calculated by prescription months per year. Participants were followed for a mean duration of 47 months. Results Participants were 94.7% men and had a mean age of 58.9 years. Nearly all used primary care (99.2%), 37.1% used pain-related specialty care, and 33.8% used mental health services. Nonopioid and opioid analgesics were the most commonly used medications (63.7% and 53.8%, respectively). Except for mental health visits, which did not differ between PTSD-only and pain+PTSD groups, the pain+PTSD group used significantly more of all categories of health care services than the pain-only and PTSD-only groups. For example, the pain+PTSD group had 7% more primary care visits (rate ratio [RR] = 1.07; 95% confidence interval [CI]: 1.05, 1.09) than the pain-only group and 46% more primary care visits than the PTSD-only group (RR = 1.46; 95% CI: 1.40, 1.52). Adjusted rates of opioid, benzodiazepine, nonopioid analgesic, and antidepressant prescriptions were higher for the pain+PTSD group than either of the comparison groups. Conclusions Our findings support our expectation that veterans with both pain and PTSD symptoms use more health care services than those with pain or PTSD symptoms alone. Research is needed to assess the health care costs associated with increases in health care utilization among these veterans.

Purpose Verbal short-term memory (STM) and working memory (WM) skills predict speech and language outcomes in children with cochlear implants (CIs) even after conventional demographic, device, and medical factors are taken into account. However, prior research has focused on single end point outcomes as opposed to the longitudinal process of development of verbal STM/WM and speech-language skills. In this study, the authors investigated relations between profiles of verbal STM/WM development and speech-language development over time. Method Profiles of verbal STM/WM development were identified through the use of group-based trajectory analysis of repeated digit span measures over at least a 2-year time period in a sample of 66 children (ages 6–16 years) with CIs. Subjects also completed repeated assessments of speech and language skills during the same time period. Results Clusters representing different patterns of development of verbal STM (digit span forward scores) were related to the growth rate of vocabulary and language comprehension skills over time. Clusters representing different patterns of development of verbal WM (digit span backward scores) were related to the growth rate of vocabulary and spoken word recognition skills over time. Conclusion Different patterns of development of verbal STM/WM capacity predict the dynamic process of development of speech and language skills in this clinical population.

Because posttraumatic stress disorder (PTSD) is both prevalent and underrecognized, routine primary care-based screening for PTSD has been implemented across the Veterans Health Administration. PTSD is frequently complicated by the presence of comorbid chronic pain, and patients with both conditions have increased symptom severity and poorer prognosis. Our objective was to determine whether the presence of pain affects diagnosis and treatment of PTSD among Department of Veterans Affairs (VA) patients who have a positive PTSD screening test. This retrospective cohort study used clinical and administrative data from six Midwestern VA medical centers. We identified 4,244 VA primary care patients with a positive PTSD screen and compared outcomes for those with and without a coexisting pain diagnosis. Outcomes were three clinically appropriate responses to positive PTSD screening: (1) mental health visit, (2) PTSD diagnosis, and (3) new selective serotonin reuptake inhibitor (SSRI) prescription. We found that patients with coexisting pain had a lower rate of mental health visits than those without pain (hazard ratio: 0.889, 95% confidence interval: 0.821-0.962). There were no significant differences in the rate of PTSD diagnosis or new SSRI prescription between patients with and without coexisting pain.

OBJECTIVE: Inadequate preparation of the bowel for colonoscopy can result in both missed pathological lesions and cancelled procedures. We looked prospectively at the quality of colonic preparation and evaluated potential associations between specific patient characteristics and inadequate colonic preparation. METHODS: Data were gathered on consecutive patients presenting for colonoscopy who received either a polyethylene glycol lavage or oral sodium phosphate bowel preparation. Patient demographic and medical history information was gathered before scheduled colonoscopy. The endoscopist evaluated the preparation quality during the procedure. Complete data were gathered on 649 of 714 eligible patients (90.8%). Possible predictors of inadequate colonic preparation were analyzed using univariate statistics and multivariate logistic regression models. RESULTS: An inadequate colonic preparation was reported in 21.7% of observed colonoscopies. Only 18% of patients with an inadequate colonic preparation reported a failure to adequately follow preparation instructions. A later colonoscopy starting time, a reported failure to follow preparation instructions, inpatient status, a procedural indication of constipation, taking tricyclic antidepressants, male gender, and a history of cirrhosis, stroke or dementia were all independent predictors of an inadequate colon preparation (all p p CONCLUSION: Several patient characteristics were significantly associated with colonic preparation quality independent of preparation type, compliance with preparation instructions, and procedure starting time. This information may help to identify patients at an increased risk for inadequate colonic preparation for whom alternative preparation protocols would be appropriate.

Hypoalbuminemic patients often have sufficient fluid accumulation to mandate diuretic therapy but are often resistant to diuresis. Studies have suggested that hypoalbuminemia itself impairs delivery of effective amounts of diuretic agent into the urine, the site of action. Therefore, administration of mixtures of albumin and loop diuretics may enhance responses. Thirteen patients with biopsy-proven cirrhosis and ascites (age, 51.2 +/- 8.1 yr; Child-Pugh score, 8.5 +/- 1.0; serum albumin concentration, 3.0 +/- 0.6 g/dl) were studied in this randomized crossover study. Sodium balance was maintained throughout the study with a metabolic diet. All patients received spironolactone, but administration of all other diuretic agents was discontinued. Each patient received all of the following four treatments intravenously: (1) 40 mg of furosemide, (2) 25 g of albumin, (3) 40 mg of furosemide and 25 g of albumin premixed ex vivo, and (4) 40 mg of furosemide and 25 g of albumin infused simultaneously into different arms. Responses were assessed by measuring urinary sodium excretion and relating the urinary furosemide excretion rate to the sodium excretion rate. Additionally, the pharmacokinetics of furosemide were assessed. Furosemide pharmacokinetics were similar for all treatment arms. Albumin alone had negligible diuretic effects. Neither albumin regimen increased the response to furosemide. Moreover, the relationship between the urinary furosemide excretion rate and the sodium excretion rate was unaffected by albumin. In conclusion, albumin failed to enhance the diuretic effects of furosemide in cirrhotic patients with ascites. Therefore, the coadministration of albumin and furosemide for the treatment of cirrhosis, and likely other hypoalbuminemic conditions, should not be used clinically.

OBJECTIVE: Most available data on screening for hepatocellular carcinoma (HCC) in patients with cirrhosis originate from Asia and Europe. These data may not be applicable to patients from the United States because of geographic variation in the underlying etiology and other factors. Our aim was to assess the risk of HCC in U.S. patients with cirrhosis undergoing standardized screening. METHODS: All cirrhotic patients evaluated for liver transplantation at our institution from January 1, 1994–December 31, 1997 were included in this study. The screening strategy included initial screening, which was offered to all patients and consisted of alpha-fetoprotein (AFP), abdominal ultrasound, and computed tomography (CT) scan, and extended screening, which was performed only on transplant-eligible patients and consisted of semiannual AFP and ultrasound. RESULTS: During the study period, 285 patients with cirrhosis were evaluated for transplantation and underwent initial screening. Of these, 166 were eligible for transplantation and underwent extended screening during a median follow-up of 15 months (range 6–42 months). Twenty-seven HCC were found, 22 during initial screening and five during extended screening. The cancer-free proportions of the cohort who underwent extended screening at 1, 2, and 3.5 yr were 98.6% ± 1.4%, 96.4 ± 1.8%, and 77.1% ± 1.7%, respectively (mean ± SE). Hepatitis C, either alone or in part, was the etiology in 63% of patients with HCC. The sensitivity of CT scan (88%) was significantly higher than AFP >20 ng/ml (62%) and ultrasound (59%) for detecting HCC (p < 0.001). CONCLUSIONS: In patients with established cirrhosis, the risk of detecting HCC is maximal at the baseline screening (7%). Hepatitis C was the most common etiology for cirrhosis in study. In U.S. patients with established cirrhosis, CT scan exhibited higher sensitivity for detecting HCC than ultrasound or AFP.

Purpose: Treatment and disease-related factors were analyzed for their influence on the outcome of patients treated definitively with irradiation (RT) for early glottic carcinoma. Methods and Materials: One hundre two patients with stage T1 or T2 glottic carcinomas were treated definitively with RT from December 1983 through September 1993. Median follow-up time was 63 months. Factors analyzed for each patients included age, sex, stage, anterior commissure involvement, surgical alternative, histologic differentiation, field size, total dose, fraction size, and total treatment time. Survival analysis methods were employed to assess the effects of these factors on local control and complication rates. Results: The 5-year local control rates by stage were as follows: T1a, 92%, T1b, 80%, T2a, 94%; and T2b, 23%. by univariate analysis, factors found to have a significant impact on local control were stage, surgical alternative, fraction size, anterior commissure involvement, and overall treatment time. By multivariate analysis, stage, field size, and fraction size were the only significant factors that independently influenced local control. Conclusion: The inferior control rate for stage T2b lesions has implications for treatment. Our study supports the conclusion of reports in the literature showing that low fration size negatively influences outcome in patients with early glottic cancer.

Purpose: To examine the outcomes of endocrine naive patients treated with tamoxifen as initial endocrine therapy for metastatic breast cancer. Data were obtained from the long-term follow-up of two previously published randomized trials. Patients and methods: All patients received tamoxifen 20 mg po in a single daily dose. Eligibility required patients to be age ≥ 18, performance status 0—3, and estrogen or progesterone receptor positive or unknown. Patients were ineligible if they had any prior endocrine therapy in either the adjuvant or metastatic setting. Results: 156 patients have been followed for a median of 8.3 years. Median age was 61 years, 83% were ≥ 50 years, 84% performance status of 0–1, 43% were both ER and PR positive, 33% had prior chemotherapy, 62% had a disease-free interval of > 2 years, and 59% had only one metastatic site. The complete (14%) and partial (6%) response rate for 147 evaluable patients was 20% (95% CI for CR + PR of 14–27%). Multivariate analysis revealed that improved response was related to soft tissue involvement and positive PR status. The majority of patients with soft tissue, nodal or lung metastases had responses noted within three months. Median time to disease progression was 6.7 months. Multivariate analysis revealed that older patients, those with one metastatic site and those with positive PR status had the longest time to progression. Median survival was 27.2 months. Better performance status, fewer metastatic sites and being PR positive were associated with significantly improved survival. Conclusion: The patient population in this series is not likely to be studied in future trials because of the wide use of tamoxifen in the adjuvant setting. In a small percentage of patients with metastatic breast cancer, tamoxifen therapy is associated with prolonged remission and survival. Pretreatment characteristics can help identify such patients.

Reaching Out and Preventing Increases in Diabetes (RAPID) is a community-based randomized trial evaluating the comparative costs and effectiveness of a group-based adaption of the DPP lifestyle intervention developed and implemented in partnership with the YMCA. RAPID enrolled adult primary care patients, with BMI 24 kg/m(2) or higher and abnormal glucose metabolism (HbA1c 5.7-6.9% or fasting plasma glucose 100-125 mg/dL). 509 participants were enrolled and randomized to one of two groups: standard clinical advice plus free-of-charge access to a group-based adaption of the DPP offered by the Y, versus standard clinical advice alone. Key outcomes for future analysis will include differences in body weight and other cardiovascular risk factors over a 24-month intervention period. At baseline, RAPID participants had a mean (SD) age of 51 ± 12.1 years, weight of 225.1 ± 56.2 lbs, and BMI of 36.9 ± 8.6 kg/m(2). 70.7% were women, 57.2% were African American, 35.4% were non-Hispanic White, and 3.2% were Hispanic. Mean HbA1c was 6.05 ± 0.34%. Additionally, 55.4% of participants had a baseline systolic blood pressure of ≥130 mmHg, 33.1% had a total blood cholesterol exceeding 200mg/dL, and 74% reported a household income of

The Asymptomatic Carotid Artery Progression Study (ACAPS) compared the usefulness of lovastatin alone or in combination with warfarin in the prevention of 3-year progression of mean maximum intimal-me

Cochlear implants (CIs) help many deaf children achieve near-normal speech and language (S/L) milestones. Nevertheless, high levels of unexplained variability in S/L outcomes are limiting factors in improving the effectiveness of CIs in deaf children. The objective of this study was to longitudinally assess the role of verbal short-term memory (STM) and working memory (WM) capacity as a progress-limiting source of variability in S/L outcomes after CI in children.Longitudinal study of 66 children with CIs for prelingual severe-to-profound hearing loss. Outcome measures included performance on digit span forward (DSF), digit span backward (DSB), and four conventional S/L measures that examined spoken-word recognition (Phonetically Balanced Kindergarten word test), receptive vocabulary (Peabody Picture Vocabulary Test ), sentence-recognition skills (Hearing in Noise Test), and receptive and expressive language functioning (Clinical Evaluation of Language Fundamentals Fourth Edition Core Language Score; CELF).Growth curves for DSF and DSB in the CI sample over time were comparable in slope, but consistently lagged in magnitude relative to norms for normal-hearing peers of the same age. For DSF and DSB, 50.5% and 44.0%, respectively, of the CI sample scored more than 1 SD below the normative mean for raw scores across all ages. The first (baseline) DSF score significantly predicted all endpoint scores for the four S/L measures, and DSF slope (growth) over time predicted CELF scores. DSF baseline and slope accounted for an additional 13 to 31% of variance in S/L scores after controlling for conventional predictor variables such as: chronological age at time of testing, age at time of implantation, communication mode (auditory-oral communication versus total communication), and maternal education. Only DSB baseline scores predicted endpoint language scores on Peabody Picture Vocabulary Test and CELF. DSB slopes were not significantly related to any endpoint S/L measures. DSB baseline scores and slopes taken together accounted for an additional 4 to 19% of variance in S/L endpoint measures after controlling for the conventional predictor variables.Verbal STM/WM scores, process measures of information capacity, develop at an average rate in the years after cochlear implantation, but were found to consistently lag in absolute magnitude behind those reported for normal-hearing peers. Baseline verbal STM/WM predicted long-term endpoint S/L outcomes, but verbal STM slopes predicted only endpoint language outcomes. Verbal STM/WM processing skills reflect important underlying core elementary neurocognitive functions and represent potential intervention targets for improving endpoint S/L outcomes in pediatric CI users.

Acute anemia may lead to erroneously low arterial reference sample concentrations of radioactive microspheres, depending on the sampling rate and the size of the artery from which the reference samples are withdrawn. Because this error would lead to falsely high cerebral blood flow values in studies involving hemodilution caused by hemorrhage and fluid resuscitation, we studied the effects of hematocrit, withdrawal rate, and vessel location and size on arterial microsphere concentrations in anesthetized adult cats. Cats were anesthetized with ketamine, isoflurane, and nitrous oxide; both brachial arteries were cannulated with polyethylene tubing, as was the abdominal aorta through the femoral artery. Sequential left atrial microsphere injections were made using several doses of each of five isotopes. The rate of reference sample withdrawal from the three sampling catheters was randomized to 1.03 mL.min-1 or 2.06 mL.min-1. We analyzed the ratio of the number of microspheres in paired reference samples using the factors hematocrit, rate of withdrawal, and site. A ratio less than 1 indicates an underestimation of arterial microsphere concentration, which would lead to erroneously high cerebral blood flow values. The procedure was repeated after isovolemic hemodilution with 10% hetastarch to hemoglobin levels approximating 85%, 70%, 55%, and 40% of baseline. No significant effects of hematocrit on ratios of microsphere concentrations existed at any withdrawal rate or site. Ratios of microsphere concentrations in reference samples withdrawn slowly (1.03 mL.min-1) from the aorta and ratios of microsphere concentrations withdrawn either rapidly (2.06 mL.min-1) or slowly from the brachial arteries were significantly (P < .001) less than 1. Hemodilution did not affect microsphere concentrations in arterial reference samples at any withdrawal site or rate and therefore does not affect the accuracy of microsphere blood flow determinations. However, slow withdrawal from a large vessel may underestimate actual microsphere concentrations.

Background. Women who do not receive adjuvant irradiation after hysterectomy for endometrial carcinoma (EC) are at risk for developing a pelvic recurrence. Disease- and treatment-related factors were examined for their impact on disease-specific survival (DSS) and pelvic control (PC) in patients with locoregional recurrences to whom salvage radiotherapy was administered. Methods. Forty-five patients with pelvic/vaginal recurrences of EC were treated at a single institution between 1973 and 1991. The median follow-up period was 89 months. Multiple patient-, disease-, and treatment-related factors were examined with univariate and multi-variate analysis for their impact on DSS and PC. Kaplan-Meier methods were used to estimate outcomes. Results. Overall DSS and PC was 51 and 54% at 5 years, respectively. Univariate analysis revealed the following factors to impact on outcome (Peg 0.05): age (DSS, PC), vaginal stage of recurrence (DSS, PC), size of recurrence (DSS, PC), time interval from hysterectomy (DSS, PC), initial grade (DSS), location of recurrence (PC), and radiation boost technique (PC). Conclusion. Women in whom endometrial cancer recurrences develop can be salvaged with aggressive radiotherapy consisting of external beam therapy followed by a radiation boost. Close follow-up after the initial hysterectomy is important because patients with low-volume recurrence limited to the vagina have the best outcome.

Vincristine (VCR) and etoposide (VP-16) have been shown to be synergistic in a murine model, and this combination was studied in a phase II trial. Eligibility required measurable disease, a performance status of 0-2, a life expectancy ofor = 2 months, an interval of at least 3 weeks since the receipt of previous radiation therapy or chemotherapy and recovery from related toxicity, no prior treatment with VCR or VP-16, and no more than two prior chemotherapy regimens (only one for treatment of metastatic disease). Treatment consisted of 0.5 mg i.v. (bolus) VCR followed by 200 mg/m2 VP-16 given over 2 h. Both drugs were given daily for 3 consecutive days every 3 weeks (total dose: VCR, 1.5 mg; VP-16, 600 mg/m2). A total of 18 patients with metastatic breast cancer were accured; 14 had adjuvant chemotherapy and 8 had chemotherapy for advanced disease. As judged by International Union Against Cancer (UICC) criteria, one complete response (CR) and three partial responses (PR) were obtained, for a CR + PR rate of 22% (95% confidence interval, 6%-48%). All responders had soft-tissue involvement only. Six patients had stable disease and 8 showed progression. The median time to treatment failure was 3.5 months, and the median survival from study entry was 8.3 months. The major toxicity was myelosuppression, with 9 patients (50%) experiencing a total WBC of1,000/mm3. Grade 2-3 neurologic toxicity was noted in 6 patients (33%) and grade 3 nausea and vomiting was noted in 5 (28%). The combination of VCR and VP-16 is active in advanced breast cancer but is not convincingly superior to either of these agents used alone.

Objective Enteric-coated (EC) high-buffered (2.5 mEq [2.5 mmol] bicarbonate per capsule) pancrelipase microsphere enzymes were compared to EC-nonbuffered pancreatic enzymes for efficacy in reducing steatorrhea in patients with cystic fibrosis. Design Prospective, randomized, controlled trial using a crossover design with each subject as his/her own control. Subjects/Setting Eighteen subjects with cystic fibrosis, who had pancreatic insufficiency and required large enzyme doses, were studied over two consecutive 7-day treatment periods. Intervention Each 7-day period consisted of 3 days at home followed by 4 days in a general clinical research center for careful control of diets, enzyme lipase doses (given at approximately 50% of the subject's usual lipase dose), and carmine red-labeled stool collections for 72-hour fecal fat balance studies. Main Outcome Measure Fecal fat excretion. Statistical Analyses Performed Differences in fat excretion, when each subject received EC–high-buffered pancrelipase vs EC-nonbuffered enzymes, were compared using linear modeling. Results Mean fat excretion decreased significantly in each subject during periods when given EC–high-buffered pancrelipase compared with periods when given EC-nonbuffered enzymes (fat excretion 18.2% vs 24.9% or fat absorption 81.8% vs 75.1%, respectively; P =0.01). Thirteen of 18 subjects (72%) excreted less fat when receiving EC–high-buffered pancrelipase whereas 10 (56%) decreased fat excretion by more than 5%, and five subjects did not respond. Conclusions EC–high-buffered pancrelipase decreased fat excretion, symbolizing improved fat absorption, when compared with EC-nonbuffered pancreatic enzymes given at equivalent, reduced (approximately 50% of usual) lipase doses in nourished subjects with cystic fibrosis and mild pulmonary disease.

Background: Endoscopic measures such as balloon dilation can relieve obstruction and improve symptoms in patients with primary sclerosing cholangitis (PSC). However, the influence of repeated endoscopy to maintain biliary patency on the survival of patients with PSC is unclear. Methods: This study evaluated the impact of endoscopic therapy on the survival of consecutive patients with PSC undergoing endoscopic therapy. During a 6-year period 63 patients underwent endoscopic therapy. After initial therapy, patients were followed for a median of 34 months. Endoscopic therapy primarily consisted of repeated balloon dilation of dominant biliary strictures. The observed survival of this cohort was estimated (Kaplan-Meier). The predicted survival of the cohort was estimated by using the Mayo Clinic survival model based on clinical information obtained within 3 months before first endoscopic therapy. The Mayo Risk Score was calculated by using the equation R=(0.03 Age, years) + (0.54 log e Bilirubin mg/dL) + (0.54 log e Aspartate aminotransferase U/mL) + (1.24 Bleed history) − (0.84 Albumin gm/dL). Results: The observed survival over 5 years was significantly higher than the predicted 5-year survival (83% vs. 65%, respectively; p = 0.027). Conclusion: These data suggest that repeated endoscopic attempts to maintain biliary patency may improve the survival of patients with PSC and dominant strictures. (Gastrointest Endosc 2001;53:308-12.)

Patients with primary sclerosing cholangitis (PSC) have a significantly increased risk of developing cholangiocarcinoma (CCA). Risk factors for developing such a complication are not well defined. We conducted a multicenter, case-control study to determine the risk factors and possible predictors for CCA in patients with PSC. The demographic, clinical, and laboratory features of 26 PSC patients with CCA diagnosed over a 7-year period at eight academic centers were compared with 87 patients with PSC but no CCA (controls). There was no statistically significant difference in demographics, smoking, signs or symptoms or complications of PSC, indices of disease severity (Mayo Risk score or Child-Pugh score), frequency or duration or complications of inflammatory bowel disease (IBD), frequency of biliary surgery, or therapeutic endoscopy between the two groups. Alcohol consumption was significantly associated with CCA in patients with PSC (odds ratio: 2.95; 95% CI: 1.04-8.3). Serum carbohydrate antigen 19-9 (CA 19-9) was significantly higher in patients with CCA than those without (177 +/- 89 and 61 +/- 58 U/mL, respectively; P =.002). A serum CA 19-9 level100 U/mL had 75% sensitivity and 80% specificity in identifying PSC patients with CCA. In conclusion, alcohol consumption was a risk factor for having CCA in PSC patients. The indices of severity of liver disease were not associated with CCA in patients with PSC. Serum CA 19-9 appeared to have good ability to discriminate PSC patients with and without CCA.

Hepatocellular carcinoma (HCC) is one of the dreaded complications of cirrhosis. Although there are no randomized controlled studies showing improved survival with screening, patients with cirrhosis are screened for HCC. Little is known about the practice of HCC screening in the United States. Our aim was to describe the practice of HCC screening in patients with cirrhosis in the United States.In March 1998, we mailed a standard questionnaire to 1021 physician members of the American Association of Study for Liver Diseases and the same questionnaire was re-sent to nonrespondents 4 weeks later.We received a response from 554 members (54%). After excluding those not involved in active adult patient care, 473 responses were eligible for analysis. Eighty-four percent of the respondents routinely screened patients with cirrhosis for HCC (screening respondents). Nearly half of the screening respondents limited the HCC screening to patients with high-risk etiologies such as hepatitis B or C or hemochromatosis. Although alpha-fetoprotein (99.7%) and ultrasound (93%) were the two most frequently used screening methods, a sizable proportion of the screening respondents (25%) used abdominal computed tomography for routine screening. On multivariate analysis, the following variables predicted screening for HCC by the respondents: seeing more than one new cirrhotic per week (odds ratio [OR]: 5.4, 95% confidence interval [CI]: 2.5-11.7); practicing for10 yr (OR: 4.0, 95% CI: 1.2-13.4); an opinion that screening is cost-effective (OR: 6.4, 95% CI: 1.6-25); an opinion that screening prolongs survival (OR: 5.7, 95% CI: 1.8-17.9); and an opinion that not screening poses malpractice liability (OR: 9.3, 95% CI: 4.2-20.8).The majority of respondents routinely screen patients with cirrhosis for HCC. Approximately half of the screening respondents limit their screening to only patients with high-risk etiologies. On multivariate analysis, several variables predicted screening for HCC by the respondents.

From the Insulin Resistance Atherosclerosis Study (IRAS), 1173 men and women of African-American, non-Hispanic white, and Hispanic ethnicity with no history of diabetes were included in an evaluation of the cross-sectional relation of habitual dietary fat intake with insulin sensitivity (S I ) as assessed by minimal-model analysis of a 12-sample, insulin-modified frequently sampled intravenous-glucose-tolerance test. Dietary intake was measured by a food-frequency interview modified to enhance sensitivity to food choices within the three ethnic groups. Percentage of energy from total fat was associated with rank of S I (S I(rank) ; r = -0.06, P = 0.03), with log fasting insulin (r = 0.10, P < 0.001), and with BMI (r = 0.10, P < 0.001). Multiple-linear-regression models included S I(rank) as the dependent variable, dietary fat (g/d) as the primary independent variable adjusted sequentially for total energy, other covariates, body mass index, and waist-hip circumference ratio (WHR). For all subjects combined, total fat intake was inversely related to S I(rank) , but this association was not significant (P = 0.14) and was attenuated by adjustment for body mass index and WHR (P = 0.44). The association of total fat (g/d) with S I(rank) differed significantly (P < 0.01) for obese compared with nonobese individuals. Higher fat intake was associated with lower S I(rank) among obese (β = -1.40, P = 0.03) but not among nonobese persons (β = 0.16, P = 0.80). Among the obese (body mass index ≤ 63), adjustment for body mass index largely accounted for the observed association of dietary fat with S I(rank) . These findings were generally consistent for monounsaturated, polyunsaturated, and saturated fats. Among individuals already at increased risk for non-insulin-dependent diabetes mellitus because of obesity, high intake of dietary fat may worsen insulin sensitivity. This effect may be mediated by the relation of dietary fat to obesity.

A select group of screened applicants initially disqualified from a four-center, primary prevention drug lipid-lowering trial because of borderline elevated serum low-density lipoprotein cholesterol (LDL-C) levels, as defined in National Cholesterol Education Program-Adult Treatment Panel I (NCEP-ATP I) guidelines, participated in a dietary intervention protocol that was incorporated into the screening phase of the trial. Seventy-seven screened applicants for the Asymptomatic Carotid Artery Progression Study entered the dietary program, which was overseen by an experienced registered dietitian at the central operations sites who collaborated with local staff at clinical sites during program implementation. NCEP-ATP I fat-modified step I diet specifications served as the basis for the intervention. The program, consisting of five sessions conducted over an 8-week period, primarily used written and audiovisual educational materials in combination with behavioral approaches. Of the original 77 participants, 36 responded to the intervention by achieving their LDL-C goal. Twenty-nine were nonresponders and 12 were dropouts. Responders achieved an average 11.7% drop in total cholesterol at the end of the 8-week program. Mean LDL-C decline paralleled total cholesterol change. High-density lipoprotein cholesterol also decreased significantly. These results were sustained for 24 of the responders attending the final screening visit approximately a month later, when another fasting blood lipid measurement was made. Participants who dropped out were more likely to be smokers. Pre- and postintervention nutrition data assessed by semiquantitative food frequency questionnaire for 20 screenees randomized into the study indicated significant reductions in total fat, saturated fat, polyunsaturated fat, and dietary cholesterol, all known to influence blood lipid levels. Similar programs may prove useful to other drug lipid-lowering trials to maximize recruitment efforts.

Objectives : To investigate the effects of hypertonic saline for resuscitation after mild hemorrhagic hypotension combined with fluid-percussion traumatic brain injury. Specifically, the effects of hypertonic saline on intracranial pressure, cerebral blood flow (radioactive microsphere method), cerebral oxygen delivery (cerebral oxygen delivery = cerebral blood flow x arterial oxygen content), and electroencephalographic activity were studied. Design : Randomized, controlled, intervention trial. Setting : University laboratory. Subjects : Thirty-four mongrel cats of either sex, anesthetized with 1.0% to 1.5% isoflurane in nitrous oxide/oxygen (70 :30). Interventions : Anesthetized (isoflurane) cats were prepared for traumatic brain injury, and then randomly assigned to the following groups : moderate traumatic brain injury only (2.7 ± 0.2 atmospheres [atm], group 1) ; mild hemorrhage (18 mL/kg) only, followed immediately by resuscitation with 10% hydroxyethyl starch in 0.9% saline in a volume equal to shed blood (group 2) ; or both traumatic brain injury (2.7 ± 0.1 atm) and mild hemorrhage, followed immediately by replacement of a volume equal to shed blood of 10% hydroxyethyl starch in 0.9% saline (group 3) ; or 3.0% saline (group 4). Measurements and Main Results : Data were collected at baseline, at the end of hemorrhage, and at 0, 60, and 120 mins after resuscitation (or at comparable time points in group 1). Intracranial pressure in group 1 was significantly increased by traumatic brain injury at the end of hemorrhage, immediately after resuscitation, and 60 mins after resuscitation (p

Measurements of intimal-medial thickness (IMT) of the carotid artery by B-mode ultrasonography are widely used as markers of atherosclerosis. This report describes empirical features of these measurements to characterize their distribution within arterial wall segments, to explore their potential as study outcome measures, and to examine their links with traditional risk factors for cardiovascular disease. Sequential transverse measurements of IMT in the carotid arteries were made in 899 participants from the Asymptomatic Carotid Artery Progression Study (ACAPS) at baseline. Data from 17 intrasegment sites in each of 12 arterial wall segments were used to describe patterns of thickness and visualization and to characterize cross-sectional area, severity, and roughness/irregularity by the intrasegment averages, maxima, and SDs of IMT, respectively. Serial correlations of IMT measurements indicated localized and diffuse features of disease. The spatial distribution of IMT had two dominant features: overall mass and mass relative to roughness. The validity of these features was demonstrated by their correlation to known risk factors for carotid atherosclerosis: body mass index, age, high-density lipoprotein cholesterol, systolic blood pressure, smoking, and sex. Both the mean and maxima of intrasegment measurements appear to be good candidates for use in clinical studies. B-mode ultrasonography has validity for the description of IMT roughness and shape. Both of these features are linked to cardiovascular risk factors, which supports the multifaceted nature of atherosclerosis.

Background: Epidemiologic evidence and meta-analyses of data from early clinical trials suggest that lowering the levels of cholesterol does not reduce the events of stroke. These analyses have not included more recent clinical trials using reductase inhibitors. Objective: To conduct a meta-analysis of the effect of reducing cholesterol levels on stroke in all reported clinical trials of primary (n=4) and secondary (n=8) prevention of coronary heart disease that used reductase inhibitor monotherapy and provided information on incident stroke. Results: Analysis of combined data from primary and secondary prevention trials showed a highly statistically significant reduction of stroke associated with the use of reductase inhibitor monotherapy (27% reduction in stroke; P =.001). Analysis of secondary prevention trials alone disclosed a similar statistically significant effect (32% reduction in stroke; P =.001). A smaller nonsignificant reduction in stroke was noted in the primary prevention trials (15% reduction in stroke; P =.48). Conclusions: Reductase inhibitors now in use for lowering cholesterol levels are more potent and have fewer side effects than the cholesterol-lowering agents previously available. They appear to reduce stroke, most notably in patients with prevalent coronary artery disease, which may be partly due to the effects of lowering the levels of cholesterol on the progression and plaque stability of extracranial carotid atherosclerosis or the marked reduction of incident coronary heart disease associated with treatment. Arch Intern Med. 1997;157:1305-1310