Predictors of inadequate bowel preparation for colonoscopy.

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 < 0.05). A procedural indication of previous polypectomy was a negative predictor of inadequate colonic preparation (p < 0.05). 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.

Impact of endoscopic therapy on the survival of patients with primary sclerosing cholangitis.

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.

Sequencing diet and exercise programs for African American women with diabetes.

PURPOSE: This study was designed to compare the effects of 2 programs that present diet and exercise components in a different sequence. METHODS: At an urban YMCA, African American women with type 2 diabetes, aged 30 to 65, were randomly assigned to either 10 weekly sessions about healthy eating followed by 6 weekly sessions about exercise or to the reverse sequence. Sessions consisted of small group discussions and physical activity or food tasting. Primary outcomes were attendance, percent of calories consumed from fat, fruit and vegetable intake, and minutes of exercise per week. Measures were taken at baseline, and 4 and 12 months after the program. RESULTS: The only group difference found at the 12-month follow-up was in diastolic blood pressure. Time effects for both groups combined included an increase in minutes of activity, an increase in vegetable intake, and a decrease in percent of calories consumed from fat. CONCLUSIONS: This study does not provide definitive evidence of which sequence may be best to bring about behavior change. The effects of sequencing difficult behavioral changes such as diet modification and establishing an exercise habit deserve further study.

Cholangiocarcinoma in patients with primary sclerosing cholangitis: a multicenter case-control study.

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 level > 100 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.

Screening for hepatocellular carcinoma in patients with advanced cirrhosis.

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.

Screening for hepatocellular carcinoma in patients with cirrhosis in the United States: results of a national survey.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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 for < 10 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). CONCLUSIONS: 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.

Definitive radiotherapy for early glottic carcinoma: prognostic factors and implications for treatment.

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 hundred 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 patient 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 fraction size negatively influences outcome in patients with early glottic cancer.

Reductase inhibitor monotherapy and stroke prevention.

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.

Definitive radiotherapy for early glottic carcinoma: prognostic factors and implications for treatment.

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 hundred 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 patient 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. CONCLUSIONS: The inferior control rate for stage T2b lesions has implications for treatment. Our study supports the conclusions of reports in the literature showing that low fraction size negatively influences outcome in patients with early glottic cancer.

Tamoxifen as initial endocrine therapy for metastatic breast cancer: long term follow-up of two Piedmont Oncology Association (POA) trials.

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 > or = 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 > or = 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.

Differences in insulin suppression of free fatty acid levels by gender and glucose tolerance status. Relation to plasma triglyceride and apolipoprotein B concentrations. Insulin Resistance Atherosclerosis Study (IRAS) Investigators.

Most discussions of relations of insulin resistance to coronary heart disease risk factors have focused on insulin-stimulated glucose uptake, but insulin suppression of plasma free fatty acid (FFA) levels is also important in lipid and lipoprotein metabolism. To identify groups with impaired insulin suppression of FFAs, we studied a multiethnic cohort of 1521 women and men at four US centers that comprise the Insulin Resistance Atherosclerosis Study (IRAS): 682 with normal glucose tolerance, 352 with impaired glucose tolerance, and 487 with non-insulin-dependent diabetes. The FFA level 2 hours after a 75-gm oral glucose load adjusted for fasting FFAs was used as the measure of insulin suppression. After adjustment for age, center, ethnicity, body mass index, and fasting and 2-hour insulin levels, 2-hour FFA levels were significantly higher in men than women and in persons with impaired glucose tolerance and non-insulin-dependent diabetes mellitus versus normal glucose tolerance. The gender difference was largely accounted for by differences in central obesity as measured by waist-hip ratio; the difference by glucose tolerance status was not affected by central obesity, suggesting a different mechanism. In multivariate regression analyses, 2-hour FFA levels were strongly related to fasting triglyceride and apoB levels, respectively, after adjustment for age, fasting and 2-hour insulin concentrations, and fasting FFA concentrations. In summary, elevated plasma apoB and triglyceride concentrations associated with male gender and with glucose intolerance are partly accounted for by differences in the ability of insulin to suppress FFA concentrations.

Dietary fat and insulin sensitivity in a triethnic population: the role of obesity. The Insulin Resistance Atherosclerosis Study (IRAS)

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 (SI) 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 SI (SI(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 SI(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 SI(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 SI(rank) differed significantly (P < 0.01) for obese compared with nonobese individuals. Higher fat intake was associated with lower SI(rank) among obese (beta = -1.40, P = 0.03) but not among nonobese persons (beta = 0.16, P = 0.80). Among the obese (body mass index < or = 63), adjustment for body mass index largely accounted for the observed association of dietary fat with SI(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.

Ankle flexibility and injury patterns in dancers.

Lower-extremity injuries are common among dancers and cause significant absences from rehearsals and performances. For this study of lower-extremity injuries in 101 ballet and 47 modern dance students, injuries requiring medical attention sustained over 1 academic year were associated with the following data obtained at the beginning of the school year: ankle flexibility, sex, dance discipline, previous injury, body mass index, and years of training. Eighty-three of the 148 students (age range, 12 to 28 years) reported prior lower-limb injuries, the most common being ankle sprains (28% of all dancers). Previous leg injuries correlated significantly with lower dorsiflexion measurements and with more new injuries. Female students had greater ankle and first metatarsophalangeal flexibility. Modern dancers had greater ankle inversion. Ninety-four students sustained 177 injuries during the study, including 75 sprains or strains and 71 cases of tendinitis. Thirty-nine percent (N = 69) were ankle injuries; 18% (N = 33) were knee injuries; 23% (N = 40) were foot injuries; and 20% (N = 35) were either hip or thigh injuries. Sixty-seven percent (N = 78) of the injured students were ballet dancers. Age, years of training, body mass index, sex, and ankle range of motion measurement had no predictive value for injury; previous injury and dance discipline both correlated with increased risk of injury.

Validation of self-reported breast and cervical cancer screening tests among low-income minority women.

The objective of the Forsyth County Cancer Screening Project is to assess barriers to breast and cervical cancer screening among low-income women and to develop an educational program to address these barriers. To properly assess the barriers, it was first necessary to determine if self-reported rates of breast and cervical cancer screening were accurate. All women who participated in the baseline survey (n = 555) were asked to provide information regarding if, where, and when they had obtained mammograms and Pap smears. Identified health care facilities were then contacted to verify this information. Approximately 80% of responses were verified for at least one of the exams with the information provided. For mammography, 77% of self-reports were correct, whereas 67% of self-reports of Pap smear screening were correct (kappa = 0.54 and 0.15, respectively). For both tests, women thought they had received them more recently than they actually had, by an average of 3 months for mammography and 23 months for Pap smears. Using validated reports of screening did not substantially change identified predictors of screening for mammography. For Pap smear screening, however, most of the identified predictors of screening became nonsignificant when medical chart reports were used instead of self-reports, suggesting that caution should be used in relying on self-reports to design programs to improve cervical cancer screening practices.

A cloud adult: the Staphylococcus aureus-virus interaction revisited.

BACKGROUND: Nasal carriage of Staphylococcus aureus is common among health care workers, but outbreaks caused by such carriers are relatively uncommon. We previously reported outbreaks of S. aureus skin infections that affected newborn infants and were attributed to an S. aureus nasal carrier who had had an associated upper respiratory tract infection (UR) during the outbreak period. OBJECTIVE: To investigate the contribution of a nasal methicillin-resistant S. aureus (MRSA) carrier (physician 4) who contracted a URI to an outbreak of MRSA infections that involved 8 of 43 patients in a surgical intensive care unit during a 3-week period. DESIGN: An epidemiologic study of an outbreak of MRSA infections and a quantitative investigation of airborne dispersal of S. aureus associated with an experimentally induced rhinoviral infection. SETTING: A university hospital. PARTICIPANTS: 43 patients in a surgical intensive care unit and 1 physician. MEASUREMENTS: Molecular typing was done, and risk factors for MRSA colonization were analyzed. Agar settle plates and volumeric air cultures were used to evaluate the airborne dispersal of S. aureus by physician 4 before and after a rhinoviral infection and with or without a surgical mask. RESULTS: A search for nasal carriers of MRSA identified a single physician (physician 4); molecular typing showed that the MRSA strain from physician 4 and those from the patients were identical. Multivariate logistic regression analysis identified exposure to physician 4 and duration of ventilation as independent risk factors for colonization with MRSA (P < or = 0.008). Air cultures showed that physician 4 dispersed little S. aureus in the absence of a URI. After experimental induction of a rhinovirus URI, physician 4's airborne dispersal of S. aureus without a surgical mask increased 40- fold; dispersal was significantly reduced when physician 4 wore a mask (P < or = 0.015). CONCLUSIONS: Physician 4 became a "cloud adult," analogous to the "cloud babies" described by Eichenwald and coworkers who shed S. aureus into the air in association with viral URIs. Airborne dispersal of S. aureus in association with a URI may be an important mechanism of transmission of S. aureus.

[Reduction of cardiovascular events with pravastatin. A pooled analysis of clinical events within the scope of the Pravastatin Atherosclerosis Intervention Program]. / Reduktion kardiovaskulärer Ereignisse unter Pravastatin. Eine gepoolte Analyse klinischer Ereignisse im Rahmen des Pravastatin-Atherosklerose-Interventions-Programms.

BACKGROUND: It has been documented that the HMG coenzyme A reductase inhibitors, or statins, can decrease cardiovascular events and mortality in patients with clinical coronary disease and moderately to severely elevated lipid levels. Additional data are required to demonstrate a reduction of vascular events in coronary patients with less than severely elevated lipid levels and in subgroups of this population. METHODS AND RESULTS: Clinical data from four atherosclerosis regression trials that evaluated pravastatin were pooled for a predetermined analysis of the effect of that agent on the risk of coronary events. All trials were double-masked, placebo-controlled designs that used pravastatin as monotherapy for 2 to 3 years. The 1891 participants in the trials had evidence of atherosclerosis and mildly to moderately elevated lipid levels. For fatal or nonfatal myocardial infarction, there was a 62% reduction in events attributable to pravastatin (p = .001). This effect was evident in younger and older patients, men and women, and patients with and without histories of hypertension and prior infarction. There was a 46% reduction in all-cause mortality (p = 17), which, although not statistically significant, is consistent with the results of other statin trials. There also was a 62% reduction in the risk of fatal or nonfatal stroke (p = .054). CONCLUSIONS: These pooled results provide strong evidence that pravastatin reduces the risk of cardiovascular events in patients with atherosclerotic disease and mildly to moderately elevated lipid levels. The benefit for reducing myocardial infarction is evident in older and younger patients, men and women, and patients with and without histories of hypertension and prior infarction.

Maximizing recruitment efforts in a drug lipid-lowering trial with dietary intervention to lower LDL cholesterol.

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.

Hypertonic saline does not improve cerebral oxygen delivery after head injury and mild hemorrhage in cats.

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 < .02 vs. baseline). In group 2, intracranial pressure increased significantly only immediately after resuscitation (p < .0001 vs. baseline). Groups 3 and 4 exhibited higher, although statistically insignificant, intracranial pressure increases at 60 and 120 mins after resuscitation. During resuscitation, cerebral blood flow increased significantly (p < .02 vs. baseline) in the uninjured cats. In contrast, cerebral blood flow failed to increase during resuscitation in the cats subjected to traumatic brain injury before hemorrhage and resuscitation. Although cerebral oxygen delivery in group 2 decreased significantly immediately, 60 mins, and 120 mins after resuscitation (p < .001 vs. baseline) both groups 3 and 4 had significantly lower cerebral oxygen delivery at 60 and 120 mins after resuscitation (p < .01 and p < .005, respectively, vs. group 1 at 60 mins after resuscitation, and p < .01 and p < .01, respectively, vs. group 1 at 120 mins after resuscitation). CONCLUSIONS: After a combination of hemorrhage and traumatic brain injury, neither 10% hydroxyethyl starch nor 3.0% hypertonic saline restored cerebral oxygen delivery. Although neither trauma alone nor hemorrhage alone altered electroencephalographic activity, the combination produced significant decreases in electroencephalographic activity at 60 and 120 mins after resuscitation in groups 3 and 4, suggesting that cerebral oxygen delivery is inadequately restored by either resuscitation fluid. Therefore, traumatic brain injury abolished compensatory cerebral blood flow increases to hemodilution, and neither hydroxyethyl starch nor 3.0% hypertonic saline restored cerebral blood flow, cerebral oxygen delivery, or electroencephalographic activity after hemorrhagic hypotension after traumatic brain injury.

Reduction in cardiovascular events during pravastatin therapy. Pooled analysis of clinical events of the Pravastatin Atherosclerosis Intervention Program.

BACKGROUND: It has been documented that the HMG coenzyme A reductase inhibitors, or statins, can decrease cardiovascular events and mortality in patients with clinical coronary disease and moderately to severely elevated lipid levels. Additional data are required to demonstrate a reduction of vascular events in coronary patients with less than severely elevated lipid levels and in subgroups of this population. METHODS AND RESULTS: Clinical data from four atherosclerosis regression trials that evaluated pravastatin were pooled for a predetermined analysis of the effect of that agent on the risk of coronary events. All trials were double-masked, placebo-controlled designs that used pravastatin as monotherapy for 2 to 3 years. The 1981 participants in the trials had evidence of atherosclerosis and mildly to moderately elevated lipid levels. For fatal or nonfatal myocardial infarction, there was a 62% reduction in events attributable to pravastatin (P = .001). This effect was evident in younger and older patients, men and women, and patients with and without histories of hypertension and prior infarction. There was a 46% reduction in all-cause mortality (P = .17), which, although not statistically significant, is consistent with the results of other statin trials. There also was a 62% reduction in the risk of fatal or nonfatal stroke (P = .054). CONCLUSIONS: These pooled results provide strong evidence that pravastatin reduces the risk of cardiovascular events in patients with atherosclerotic disease and mildly to moderately elevated lipid levels. The benefit for reducing myocardial infarction is evident in older and younger patients, men and women, and patients with and without histories of hypertension and prior infarction.