Antidepressant pharmacotherapy: economic evaluation of fluoxetine, paroxetine and sertraline in a health maintenance organization

The present study was designed to compare direct health service expenditures, for the treatment of depression, among patients enrolled in a health maintenance organization, and prescribed one of three selective serotonin reuptake inhibitors, fluoxetine, paroxetine or sertraline. Information regarding depression-related health service use was derived from the computer archive of a network-model health maintenance organization system serving 700,000 beneficiaries. A total of 744 health maintenance organization beneficiaries were found to satisfy the study selection criteria. Multivariate regression analysis was used to determine the incremental influence of selected demographic, clinical, financial and provider characteristics on health service expenditures related to the treatment of depression (ICD-9-CM, or DSM-IV code 296.2) 1 year after the start of antidepressant pharmacotherapy. Multivariate findings indicate that treatment with paroxetine increases average expenditures for physician visits ($31.93; P < or = 0.05), psychiatric visits ($19.33; NS), laboratory tests ($2.35; P < or = 0.05), hospitalizations ($85.33; P < or = 0.05), psychiatric hospitalizations ($82.01; P < or = 0.05), and antidepressant pharmacotherapy ($63.72; P < or = 0.05), for a total per capita increase in health service use of $284.68 (P < or = 0.05), compared with treatment with fluoxetine. Sertraline treatment increases average expenditures for physician visits ($21.74; P < or = 0.05), psychiatric visits ($56.79; P < or = 0.05), laboratory tests ($1.21; P < or = 0.05), hospitalizations ($70.59; P < or = 0.05), psychiatric hospitalizations ($95.75; P < or = 0.05), and antidepressant pharmacotherapy ($69.85; P < or = 0.05), for a total per capita increase in health service use of $315.96 (P < or = 0.05), compared with treatment with fluoxetine. Economic comparisons between paroxetine and sertraline did not demonstrate any significant differences in expenditures for the health services examined.     

A double-blind study of paroxetine, fluoxetine, and placebo in outpatients with major depression

Human milk has a higher concentration of nucleotides than bovine milk which is the source of most infant formulas. As the composition of human milk is considered the 'gold standard,' an increasing number of infant formulas are supplemented with nucleotides. This review summarises the biology of human milk nucleotides and evaluates the studies which investigated the clinical benefits of feeding infants with nucleotide-supplemented formulas. Although dietary nucleotides have been suggested to have beneficial gastrointestinal and immunological effects, nucleotide-supplemented formula feeding has not been shown to confer the same benefits as breast feeding, and randomised controlled trials have yet to prove that healthy term infants fed nucleotide-supplemented formulas compared to those fed nonsupplemented formulas, have accelerated physical growth and neurological development, better growth and development of their gastrointestinal tract resulting in improved digestive and absorptive functions, enhanced development of their immune system resulting in increased resistance to infection and lower bacterial and viral infection rates during infancy, and a more favourable intestinal microflora associated with a lower rate of infectious diarrhoea. However, a randomised controlled trial has reported that term infants with severe intrauterine growth retardation do have better catch-up growth with nucleotide supplementation. The hypothesis that nucleotides are semi-essential nutrients needs to be further studied, in particular in the presence of prematurity, fetal growth retardation, intestinal injury and limited nutrient intake. As no deleterious effects have been reported with the use of nucleotide-supplemented formulas, the first of which was introduced over 30 years ago, such products are considered safe when nucleotides are supplemented to an amount equivalent to the free nucleotide concentration of human milk. More basic and clinical research studies are awaited to further define the biology and role of human milk nucleotides, and to critically assess the potential benefits and appropriate level of nucleotide supplementation of infant formula.     

EPIBACDIAL: a multicenter prospective study of risk factors for bacteremia in chronic hemodialysis patients

Bacteremic infections are a major cause of mortality and morbidity in chronic hemodialysis patients. New developments in managing these patients (erythropoietin therapy, nasal mupirocin, long-term implanted catheters, and synthetic membranes) may have altered the epidemiologic patterns of bacteremia in dialysis patients. This multicenter prospective cross-sectional study was carried out to determine the current incidence of and risk factors for bacteremia in chronic hemodialysis patients in France. A total of 988 adults on chronic hemodialysis for 1 mo or longer was followed up prospectively for 6 mo in 19 French dialysis units. The factors associated with the development of at least one bacteremic episode over 6 mo were determined using the multivariate Cox proportional hazards model. Staphylococcus aureus (n=20) and coagulase-negative staphylococci (n=15) were responsible for most of the 51 bacteremic episodes recorded. The incidence of bacteremia was 0.93 episode per 100 patient-months. Four risk factors for bacteremia were identified: (1) vascular access (catheter versus fistula: RR=7.6; 95% CI, 3.7 to 15.6); (2) history of bacteremia (> or =2 versus no previous episode: RR=7.3; 95% CI, 3.2 to 16.4); (3) immunosuppressive therapy (current versus no: RR=3.0; 95% CI, 1.0 to 6.1); and (4) corpuscular hemoglobin (per 1 g/dl increment: RR=0.7; 95% CI, 0.6 to 0.9). Catheters, especially long-term implanted catheters, were found to be the leading risk factor of bacteremia in chronic hemodialysis patients. There was a trend toward recurrence of bacteremia that was not associated with chronic staphylococcal nasal carriage. Synthetic membranes were not associated with a lower risk of bacteremia in this population of well dialyzed patients, but anemia linked to resistance to erythropoietin appeared to be a possible risk factor for bacteremia.     

A prospective, multicenter study of a pneumonia practice guideline

Two-dimensional 1H detected 13C NMR spectroscopy has been used to study the intracellular metabolism of [3-(13)C]pyruvate in Halobacterium salinarium. The method, resulting in considerable improvement in spectral resolution and signal-to-noise ratio, is well suited for studying transient metabolic intermediates. Pyruvate utilization by the bacterium is a double exponential function with rate constants of 49.13 and 4.67x10(-3) per min. The relative 13C enrichment is the fastest for C-3 glutamate. Glutamate C-4 labeling decreases initially and increases later on during incubation, while glutamine C-3 is high to begin with and exhibits a declining trend. The glutamate labeling indicates a high initial flux through pyruvate carboxylase and extensive randomizing of the label in the tricarboxylic acid cycle.     

Histamine release in sepsis: a prospective, controlled, clinical study

OBJECTIVE: To determine if histamine release occurs in clinical sepsis. DESIGN: Prospective, controlled, clinical study. SETTING: Interdisciplinary intensive care unit and trauma ward. PATIENTS: Sepsis was confirmed in 20 patients (test group) by the criteria of the Veterans Administration Systemic Sepsis Cooperative Study Group (1987) and was verified by positive blood culture. In addition, patients were scored by the Elebute and Stoner Sepsis Score (1983), as modified by Dionigi et al (1985). A concomitant control group consisted of 20 postoperative patients with non-life-threatening trauma to the extremities and without signs of local or systemic infection. INTERVENTIONS: Observational study. Blood samples were collected for determination of plasma histamine concentrations in both groups at the time of study entry and on five succeeding days. MEASUREMENTS AND MAIN RESULTS: The patients were well matched, and the groups were not significantly different for all criteria known to influence histamine release. Comparison of the median values of each group on days 1 through 5 demonstrated significantly higher plasma histamine values in the test group on days 1 through 4, but these values were no longer significantly higher on day 5. While none of the nonseptic control patients achieved a plasma histamine concentration of > 1 ng/mL (the concentration of which was considered to be the pathologic cutoff point representing histamine release), these values (i.e., > 1 ng/ mL) were found in nine of 20 test group patients. In the test group, nonsurvivors (n = 9) had significantly higher plasma histamine concentrations than survivors (n = 11) throughout the whole study and eight of nine nonsurvivors showed a plasma histamine concentration of > 1 ng/mL. Correlation of plasma histamine concentrations on day 1 to sepsis severity (initial Sepsis Score) showed that all but one patient with a combined low Sepsis Score (< 20 points) and histamine concentration of < 1 ng/mL survived, while all patients with a Sepsis Score of > 20 points and histamine release (plasma histamine concentration of > 1 ng/mL) died. CONCLUSION: Increased histamine concentrations were shown to be causally associated (contributory determinant) with sepsis.     

One year real world prospective follow-up study of a major depressive episode of patients treated with paroxetine and pindolol or paroxetine for 6 weeks

Among cochlear implant candidates there are patients who have abnormal middle and/or inner-ear conditions that make them unsuitable for implantation. Insertion of a foreign body may also be contraindicated in the setting of an existing or potential intracranial communication, or when the ear is prone to infection. Five patients presented with such unfavorable conditions. These included a Mondini dysplasia with persistent cerebrospinal fluid leak, an atretic mastoid with meningocele, chronic otitis media, a transverse petrous bone fracture, and a temporal bone adenoma. All patients underwent subtotal petrosectomies and cochlear implantations. In four cases implantation was performed concomitantly with subtotal petrosectomy, while the remaining case required a two-stage procedure. No complications occurred. The technique is described in detail, and the cases and the indications for surgery are discussed. By obliterating and isolating the tympanomastoid cleft from the outer environment and utilizing the technique of subtotal petrosectomy, a broader spectrum of patients can now be implanted safely.     

Headache in acute cerebrovascular ischemic disease: a prospective clinical study of 195 patients

BACKGROUND: Headache is a little known aspect in the study of acute ischemic cerebrovascular disease (AICVD). METHODS: To contribute to the knowledge of the clinical characteristics of headache in the different nosologic entities of AICVD a prospective study was performed in 195 patients consecutively studied by CT scan and/or cerebral MRI. RESULTS: There was headache in 32% of the total and in 41% of the thrombotic infarctions, 39% of the cardioembolisms, 26% of the transient ischemic attacks (TIA) and 23% of the lacunar infarcts. The mean duration was 25 +/- 28 hours. Headache was focal in 74% of the cases and of slight or moderate intensity in 74%. Headache was significantly more common in thrombotic infarctions than in lacunar ones (p < 0.05). It was more frequent when the topography is vertebrobasilar (57.5%), in comparison with carotid (21%) or undetermined (17.5%) (p < 0.0001). Headache was more common when topography was cortical (56.5%) in comparison with subcortical (26.5%) (p < 0.005). Eight per cent of the patients presented sentinel headache: 22% of the cardioembolic infarctions, 7% of the lacunars, 6.5% of the TIA and 5.5% of the thrombotic. CONCLUSIONS: Headache in acute ischemic cerebrovascular disease is not uncommon predominating in thrombotic infarctions and cardioembolisms of cortical topography and of vertebrobasilar vascular territory.     

Uremic pericarditis: a prospective echocardiographic and clinical study

During a 14 month period 59 male patients with chronic renal failure who were candidates for chronic hemodialysis (HD) were evaluated clinically and echocardiographically for pericarditis. All were evaluated prospectively prior to or at the initiation of HD. Definite pericarditis was present in 8, all of whom were severely uremic and required initiation of HD on a semiemergent basis rather than electively (i.e., preselected level of renal function). In 6 of these 8, pericardial effusion responded to dialysis alone, one required pericardiectomy because of hypotension complicating dialysis, and one expired during a right atriogram. Patients dialyzed on an elective basis were all free of pericarditis at the initiation of HD. Pericarditis arising some months after the initiation of HD was a less frequent problem. It is concluded that (a) the incidence of pericarditis in the uremic state is decreased by early initiation of HD before advanced uremic symptoms have developed; (b) pericarditis present at the initiation of HD usually but not always is resolved with the initiation of HD; (c) echocardiography is an important clinical and epidemiological toole to investigate pericarditis in uremic patient populations.     

A prospective, longitudinal, multicenter study of service utilization and costs in fibromyalgia

OBJECTIVE: To study, for the first time, service utilization and costs in fibromyalgia, a prevalent syndrome associated with high levels of pain, functional disability, and emotional distress. METHODS: Five hundred thirty-eight fibromyalgia patients from 6 rheumatology centers were enrolled in a 7-year prospective study of fibromyalgia outcome. Patients were assessed every 6 months with validated, mailed questionnaires which included questions regarding fibromyalgia symptoms and severity, utilization of services, and work disability. RESULTS: Fibromyalgia patients averaged almost 10 outpatient medical visits per year, and when nontraditional treatments were considered, this number increased to approximately 1 visit per month. Patients were hospitalized at a rate of 1 hospitalization every 3 years. In each 6-month study period, patients used a mean of 2.7 fibromyalgia-related drugs. Costs increased over the course of the study. The mean yearly per-patient cost in 1996 dollars was $2,274. However, results were skewed by high utilizers, and many patients used few services and had limited costs. Total costs and utilization were independently associated with the number of self-reported comorbid or associated conditions, functional disability, and global disease severity. Compared with patients with other rheumatic disorders, those with fibromyalgia were more likely to have lifetime surgical interventions, including back or neck surgery, appendectomy, carpal tunnel surgery, gynecologic surgery, abdominal surgery, and tonsillectomy, and were more likely than other rheumatic disease patients to report comorbid or associated conditions. Almost 50% of hospitalizations occurring during the study were related to fibromyalgia-associated symptoms. CONCLUSION: The average yearly cost for service utilization among fibromyalgia patients is $2,274. Fibromyalgia patients have high lifetime and current rates of utilization of all types of medical services. They report more symptoms and comorbid or associated conditions than patients with other rheumatic conditions, and symptom reporting is linked to service utilization and, to a lesser extent, functional disability and global disease severity.     

Hospital mortality in women and men with acute cardiac ischemia: a prospective multicenter study

OBJECTIVES: This study sought to determine gender differences in hospital mortality in patients with acute cardiac ischemia. BACKGROUND: It is unclear why women experience higher mortality from acute myocardial infarction (AMI) than men and whether this applies to all patients with acute ischemia. METHODS: We analyzed data from a prospective multicenter study involving patients presenting to the emergency department (ED) with symptoms suggestive of acute ischemia. RESULTS: Of 10,783 patients, 5,221 (48.4%) were women. Mean age was 60.5 years for women and 56.9 for men (p < 0.001). Women had more hypertension (54.6% vs. 45.9%, p < 0.001) and diabetes (23.3% vs. 17.0%, p < 0.001) than men but fewer previous AMIs (21.1% vs. 28.9%, p < 0.001). Acute ischemia was confirmed in 1,090 women (20.8%) and 1,451 men (26.1%, p < 0.001), including AMI in 322 women (6.2%) and 572 men (10.3%, p < 0.001). Women with an AMI were in a higher Killip class than men: class I in 60.3% versus 72.2%, class II in 19.3% versus 16%, class III in 15.5% versus 8.7% and class IV in 5% versus 3.1%, respectively (p = 0.001). There was no significant difference in mortality from acute ischemia between genders (4.0% vs. 3.5%, p = 0.6), but there was a trend for higher AMI mortality in women (10.3% vs. 7.4%, p = 0.1). After controlling for age, diabetes, heart failure and presenting blood pressure, gender did not predict mortality from acute ischemia (odds ratio 0.9, 95% confidence interval 0.5 to 1.4, p = 0.5). CONCLUSIONS: Among patients presenting to the ED with acute cardiac ischemia, gender does not appear to be an independent predictor of hospital mortality. The trend for higher mortality in women from AMI can be explained by their older age, greater frequency of diabetes and higher Killip class on presentation.     

Lung function and clinical outcome in postpolio patients: a prospective cohort study during 11 years

Inositol 1,2,3,5,6-pentakisphosphate (Ins(1,2,3,5,6)P5) 5-phosphatase present in fetal calf thymus has been partially purified. This enzyme was inhibited dose-dependently by different thiol modifiers like N-ethylmaleimide (NEM), p-chloromercuribenzene sulfonate (PCMBS), diamide, and phenylarsine oxide (PAO). The inhibition by PCMBS and diamide was protected by preincubation with dithiothreitol (DTT) and the phosphatase substrate, Ins(1,2,3,5,6)P5. Diamide, a compound that specifically modifies vicinal thiol groups, also blocked the 5-phosphatase dose-dependently. Specificity of this blockade was proven by using dimercaptopropanol (DMP), a compound known to protect vicinal thiol groups. DMP prevented the enzyme from inhibition by diamide. These data suggest that vicinal thiols are involved in Ins(1,2,3,5,6)P5 5-phosphatase activity.     

Prevention of postoperative abdominal adhesions by a sodium hyaluronate-based bioresorbable membrane: a prospective, randomized, double-blind multicenter study

Two populations of hydrogen protons exist in magnetic resonance imaging: free protons and bound protons. Bound protons do not contribute to normal MR signal because they resonate somewhat off the center frequency of water. A special pulse sequence called magnetization transfer contrast (MTC) was developed to compensate for this off-resonance limitation. A saturation transfer of bound protons occurs during MTC, enabling a transfer of energy to the free proton pool and thereby contributing to the overall MR signal. This article describes MTC, reviews its applications and explains how it improves lesion conspicuity, small vessel detail and background suppression.     

Itraconazole maintenance treatment for histoplasmosis in AIDS: a prospective, multicenter trial

The expression of cytokeratins (CKs) in normal cervical epithelium, low grade squamous intraepithelial lesions (SIL), high grade SILs and squamous cell carcinoma (SCC) were analyzed using four different monoclonal antikeratin antibodies. In normal cervical epithelium, CK 18 showed strong immunoreactivity in basal and parabasal layers. CK 19 and 14 were expressed only in the basal layer while CK 13 was found selectively n the spinal cells. As the lesions progressed from low grade SIL to high grade SIL, immunoreactivity of CK 18, 19 and 14 in the basal cell compartment increased while the expression of CK 13 decreased. In SCC, as well-differentiated tumors showed decreased immunoreactivity for CK 18, 19 and 14 with CK 13 showing a strong and focal (localized) immunoreactivity. Undifferentiated carcinomas totally lacked CK 13 reactivity. Our findings therefore suggest that expression of CK 18, 19 and 14 may be directly related to tumor grade and CK 13 may be a marker of differentiation in cervical lesions.     

Radiotherapy in stage IIA and IIB testicular seminoma with reduced portals: a prospective multicenter study

PURPOSE: A prospective multicenter study was carried out to estimate the treatment outcome of radiotherapy in Stage II seminoma after the application of modern staging and radiotherapy techniques. The lower margin of the iliac field was positioned on the upper rim of the acetabulum to reduce the amount of scattered irradiation to the remaining testicle. METHODS AND MATERIALS: The study was carried out in 25 centers in Germany. Patients with pure seminoma, negative AFP-values, and retroperitoneal lymph node metastases of less than 5 cm in diameter were entered into the study. All patients received a ventrodorsal opposed field irradiation of the para-aortic and the ipsilateral iliac lymph nodes. The fields extended from the top of the 11th thoracic vertebra to the top of the acetabulum. Patients in Stage IIA (lymph nodes <2 cm ) received 30 Gy, and patients with Stage IIB (lymph nodes between 2 and 5 cm) 36 Gy total dose. RESULTS: 39 patients in Stage IIA and 19 patients in Stage IIB were evaluated. After a median observation time of 37 months all patients are alive and disease free. Recurrence free survival in stage IIA was 100%. Two patients in Stage IIB experienced a recurrence 10 and 17 months after the end of radiotherapy. The actuarial recurrence free survival estimate in Stage IIB was 94.1% for 1 year and 87.4% for 2 years. One recurrence in Stage IIB occurred in the mediastinum, one in the mediastinum, and one the lung. Both patients could be salvaged by chemotherapy. There were no pelvic recurrences. The treatment was well tolerated, with nausea being the most common side effect (56.9% Grade 1, 15.5% Grade 2, and 8.6% Grade 3). Diarrhea occurred in 15.5% (Grade 1), 15.5% (Grade 2), and 5.2% (Grade 3) of the patients. CONCLUSIONS: The outcome of para-aortic and ipsilateral iliac irradiation in Stage IIA/B testicular seminoma is excellent with the currently available staging methods and treatment facilities. The treatment is well tolerated. The lower margin of the iliacal field can be placed at the acetabulum.     

Results of biofeedback in constipated patients: a prospective study

PURPOSE: The aims of this study were to assess the results of biofeedback treatment in constipated patients and to identify variables that might be used to predict the outcome. METHOD: Twenty-eight patients (5 men; median age, 46 (range, 22-72) years) with any degree of paradoxical activation measured with thin hook needle electromyography in the external sphincter or puborectalis muscle were included. The symptom duration varied between 1 and 30 (median, 9) years. The patients had eight outpatient training sessions with electromyography-based audiovisual feedback. All patients were followed up prospectively with a validated bowel function questionnaire from which a symptom index was created. RESULTS: At three months, nine patients had no improvement and underwent other treatments. The remaining 19 patients were followed up for a median of 14 (range, 12-34) months. Twelve patients (43 percent) stated they had improved rectal emptying. A good result was associated with increased stool frequency (P < 0.05), improved symptom index (P < 0.01), and reduction of laxative use (P < 0.05). A long symptom duration, a high pretreatment symptom index, and laxative use were related to a poor result (P < 0.01-0.05). The improved group had less perineal descent (P < 0.05), and a prominent puborectalis impression on defecography tended to be more common (P = 0.06). CONCLUSION: With the use of wide inclusion criteria, biofeedback was successful in 43 percent of patients, with a treatment effect lasting at least one year. The results suggest that biofeedback should be used as the initial treatment of constipated patients with a paradoxical puborectalis contraction.     

Reduction of adhesions after uterine myomectomy by Seprafilm membrane (HAL-F): a blinded, prospective, randomized, multicenter clinical study. Seprafilm Adhesion Study Group

OBJECTIVE: To assess the safety and efficacy of Seprafilm (HAL-F), Bioresorbable Membrane, (Genzyme Corporation, Cambridge, MA) in reducing the incidence, severity, extent, and area of uterine adhesions after myomectomy. DESIGN: Prospective, randomized, blinded, multicenter study. Adhesion reduction was assessed by an independent, blinded, gynecologic surgeon who reviewed videotapes of each patient's second-look laparoscopy. SETTING: Nineteen institutions across the United States. PATIENT(s): One hundred twenty-seven women undergoing uterine myomectomy with at least one posterior uterine incision > or = 1 cm in length. INTERVENTION(s): Patients were randomized to treatment with Seprafilm or to no treatment at the completion of the myomectomy. MAIN OUTCOME MEASURE(s): The incidence, severity, extent, and area of uterine adhesions at second-look laparoscopy. RESULT(s): The incidence, measured as the mean number of sites adherent to the uterine surface, was significantly less in treated patients (4.98 +/- 0.52 [mean +/- SEM] sites) than in no treatment patients (7.88 +/- 0.48 sites) as were the mean uterine adhesion severity scores (1.94 +/- 0.14 versus 2.43 +/- 0.10; treatment versus no treatment, respectively), mean extent scores (1.23 +/- 0.12 versus 1.68 +/- 0.10), and mean area of adhesions (13.2 +/- 1.67 versus 18.7 +/- 1.66 cm2). No adverse events occurred that were judged to be related to the use of Seprafilm. CONCLUSION(s): In this multicenter study, treatment of patients after myomectomy with Seprafilm significantly reduced the incidence, severity, extent, and area of postoperative uterine adhesions. Additionally, Seprafilm treatment was not associated with an increase in postoperative complications.     

Compliance and noncompliance in patients with a functioning renal transplant: a multicenter study

BACKGROUND: Noncompliance with medication is a major cause of renal allograft failure among adult renal transplant patients. We summarize previous studies of noncompliance and report results of a large, multicenter survey designed to identify variables that (1) affect the likelihood of compliance with immunosuppressive medication regimens and (2) distinguish among noncompliant patients. METHODS: Questionnaires were distributed to 2500 patients at 56 U.S. transplant centers. Compliance was determined by patient responses to questions concerning whether, within the previous 4 weeks, one or more doses of immunosuppressive medications had been missed. Independent variables included patient and transplant characteristics, memories of dialysis, posttransplant symptoms and beliefs, and beliefs concerning the efficacy and importance of immunosuppressants. RESULTS: The incidence of noncompliance reported by the 1402 respondents was 22.4%. A logistic regression model that included age, occupation, time since transplant, and three medication-related beliefs was most predictive of the likelihood of compliance. Donor type and histories of diabetes and of infection entered the multivariate model when belief-related variables were excluded. Cluster analyses identified three distinct profiles of noncompliers: accidental noncompliers, invulnerables, and decisive noncompliers. CONCLUSIONS: Results of this study, which included nearly three times more patients than the largest previously reported study, can be used by clinicians to identify patients likely to become noncompliant, by researchers to develop randomized, prospective clinical trials of interventions designed to increase compliance, and by educators to tailor patient education programs.     

Pulmonary complications in toxic epidermal necrolysis: a prospective clinical study

BACKGROUND: Both experimental and clinical studies have shown that the increase in regional blood flow induced by acetylcholine is not completely prevented by inhibitors of the synthesis of endothelium-derived nitric oxide. To establish the role of ATP-sensitive potassium (KATP) channels and prostacyclin in mediating acetylcholine-induced increase in peripheral blood flow in humans, we assessed the effects of acetylcholine on the iliac artery blood flow velocity before and after glibenclamide, an antagonist of KATP channels, or before and after acetylsalicylic acid, an inhibitor of prostacyclin production. MATERIAL AND METHODS: Seventeen patients without evidence of peripheral vascular disease and normal coronary arteries at angiography received intra-iliac incremental bolus injections of acetylcholine (0.2, 2, 20 and 50 micrograms) via a 5F femoral sheath, at the end of routine cardiac catheterization. All injections were repeated 90 minutes after oral administration of glibenclamide (10 mg) in 10 patients of 15 minutes after i.v. infusion of acetylsalicylic acid (1000 mg) in the remaining 7 patients. Right iliac artery blood flow velocity was measured by using an intravascular 0.014-in Doppler guidewire. RESULTS: Before glibenclamide or acetylsalicylic acid administration, acetylcholine infusion increased average peak velocity by 128% (p < 0.001) and by 121% (p < 0.001), respectively. After glibenclamide or acetylsalicylic acid the increases of average peak velocity during acetylcholine infusion (by 121%, p < 0.001, and by 121%, p < 0.001, respectively) were similar (p = ns) to those observed during the control infusion. CONCLUSIONS: In man acetylcholine-induced vasodilatation in the territory supplied by the iliac artery is not prevented by glibenclamide or acetylsalicylic acid, thus suggesting that it is independent of activation of KATP channels and prostacyclin release.     

Improving intensive care: observations based on organizational case studies in nine intensive care units: a prospective, multicenter study

OBJECTIVE: To examine organizational practices associated with higher and lower intensive care unit (ICU) outcome performance. DESIGN: Prospective multicenter study. Onsite organizational analysis; prospective inception cohort. SETTING: Nine ICUs (one medical, two surgical, six medical-surgical) at five teaching and four nonteaching hospitals. PARTICIPANTS: A sample of 3,672 ICU admissions; 316 nurses and 202 physicians. MATERIALS AND METHODS: Interviews and direct observations by a team of clinical and organizational researchers. Demographic, physiologic, and outcome data for an average of 408 admissions per ICU; and questionnaires on ICU structure and organization. The ratio of actual/predicted hospital death rate was used to measure ICU effectiveness; the ratio of actual/predicted length of ICU stay was used to assess efficiency. MEASUREMENTS AND MAIN RESULTS: ICUs with superior risk-adjusted survival could not be distinguished by structural and organizational questionnaires or by global judgment following on-site analysis. Superior organizational practices among these ICUs were related to a patient-centered culture, strong medical and nursing leadership, effective communication and coordination, and open, collaborative approaches to solving problems and managing conflict. CONCLUSIONS: The best and worst organizational practices found in this study can be used by ICU leaders as a checklist for improving ICU management.