Efficacy and safety assessment of prolonged maintenance with subcutaneous rituximab in patients with relapsed or refractory indolent non-Hodgkin lymphoma: results of the phase III MabCute study.

Rituximab plus chemotherapy induction followed by rituximab maintenance for up to 2 years confers a long-term benefit in terms of progression-free survival in patients with indolent non-Hodgkin lymphoma. It is not known whether further prolonged maintenance with rituximab provides additional benefit. The phase III MabCute study enrolled 692 patients with relapsed or refractory indolent non-Hodgkin lymphoma. Patients who responded to induction with rituximab plus chemotherapy and were still responding after up to 2 years' initial maintenance with subcutaneous rituximab were randomized to extended maintenance with subcutaneous rituximab (n=138) or observation only (n=138). The primary endpoint of investigator-assessed progression-free survival in the randomized population was un-addressed by the end of study because of an insufficient number of events (129 events were needed for 80% power at 5% significance if approximately 330 patients were randomized). In total, there were 46 progression-free survival events, 19 and 27 in the rituximab and observation arms, respectively (P=0.410 by stratified log-rank test; hazard ratio 0.76 [95% confidence interval: 0.37- 1.53]). The median progression-free survival was not reached in either randomized arm. There were no new safety signals; however, adverse events were seen slightly more frequently with rituximab than with observation during extended maintenance. Maintenance for up to 2 years with rituximab after response to initial induction therefore remains the standard of care in patients with relapsed or refractory indolent non- Hodgkin lymphoma. (Clinicaltrials.gov identifier: NCT01461928).

Substitution Monotherapy With Levetiracetam vs Older Antiepileptic Drugs: A Randomized Comparative Trial.

OBJECTIVE To determine whether patients who fail their first antiepileptic drug (AED) have better neuropsychiatric and quality-of-life (QOL) outcomes if substituted to levetiracetam monotherapy compared with a second older AED. DESIGN Randomized comparative trial. Participants with partial epilepsy who had failed monotherapy with phenytoin sodium, carbamazepine, or valproate sodium were randomized to substitution monotherapy with levetiracetam or a different older AED. Assessments were performed at baseline, 3 months, and 12 months using questionnaires measuring neuropsychiatric, QOL, seizure control, AED adverse effects, and neurocognitive outcomes. SETTING Epilepsy service of a teaching hospital. PATIENTS Fifty-one patients were randomized to levetiracetam and 48 were randomized to a second older AED (25 to valproate and 23 to carbamazepine). MAIN OUTCOME MEASURES Proportions showing improvements in depression (on the Hospital Anxiety and Depression Scale) and QOL scores (on the 89-item Quality of Life in Epilepsy Inventory) at 3 months. RESULTS There were no differences between the groups in depression scores at 3 months (improvement in 17 of 43 patients [39.5%] in the levetiracetam group and 15 of 44 patients [34.1%] in the older AED group; P = .60), but a greater proportion of the older AED group improved on the 89-item Quality of Life in Epilepsy Inventory compared with the levetiracetam group (27 of 38 patients [71.1%] vs 21 of 43 patients [48.8%], respectively; P = .04). The QOL, anxiety, and AED adverse effects scores were improved in both groups at 3 and 12 months after randomization. CONCLUSIONS Substitution monotherapy in a patient experiencing ongoing seizures or tolerability issues is associated with sustained improvements in measures of QOL, psychiatric, and adverse events outcomes. Patients switched to levetiracetam do not have better outcomes than those switched to a second older AED. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12606000102572.

Baseline iron indices as predictors of hemoglobin improvement in anemic Vietnamese women receiving weekly iron-folic acid supplementation and deworming.

Iron deficiency anemia is highly prevalent among women living in rural Vietnam. However, the utility and cut-offs of indices for diagnosing iron deficiency anemia in the public health context is ill defined. We assessed the ability of iron indices to predict the hemoglobin response (HBR) to weekly iron-folic acid supplementation (WIFS) in anemic rural Vietnamese women. We compared hemoglobin, serum ferritin, and soluble transferrin receptor in a cohort of 221 non-pregnant women of reproductive age before and after 3 months of WIFS and deworming. At baseline, anemia (Hb < 120 g/L) was present in 81/221 (36.7%) of subjects. After 3 months, anemia prevalence fell to 58/221 (26.2%), and the mean hemoglobin change was +3.5 g/L (95% confidence interval, 0.9, 6.6). A hemoglobin response was observed in 50/75 (66.6%) of anemic women. A ferritin cut-off < 30 ng/mL was a more sensitive predictor of response than ferritin < 15 ng/mL.

A free weekly iron-folic acid supplementation and regular deworming program is associated with improved hemoglobin and iron status indicators in Vietnamese women.

BACKGROUND: Anemia due to iron deficiency is recognized as one of the major nutritional deficiencies in women and children in developing countries. Daily iron supplementation for pregnant women is recommended in many countries although there are few reports of these programs working efficiently or effectively. Weekly iron-folic acid supplementation (WIFS) and regular deworming treatment is recommended for non-pregnant women living in areas with high rates of anemia. Following a baseline survey to assess the prevalence of anemia, iron deficiency and soil transmitted helminth infections, we implemented a program to make WIFS and regular deworming treatment freely and universally available for all women of reproductive age in two districts of a province in northern Vietnam over a 12 month period. The impact of the program at the population level was assessed in terms of: i) change in mean hemoglobin and iron status indicators, and ii) change in the prevalence of anemia, iron deficiency and hookworm infections. METHOD: Distribution of WIFS and deworming were integrated with routine health services and made available to 52,000 women. Demographic data and blood and stool samples were collected in baseline, and three and 12-month post-implementation surveys using a population-based, stratified multi-stage cluster sampling design. RESULTS: The mean Hb increased by 9.6 g/L (95% CI, 5.7, 13.5, p < 0.001) during the study period. Anemia (Hb<120 g/L) was present in 131/349 (37.5%, 95% CI 31.3, 44.8) subjects at baseline, and in 70/363 (19.3%, 95% CI 14.0, 24.6) after twelve months. Iron deficiency reduced from 75/329 (22.8%, 95% CI 16.9, 28.6) to 33/353 (9.3%, 95% CI 5.7, 13.0) by the 12-mnth survey, and hookworm infection from 279/366 (76.2%,, 95% CI 68.6, 83.8) to 66/287 (23.0%, 95% CI 17.5, 28.5) over the same period. CONCLUSION: A free, universal WIFS program with regular deworming was associated with reduced prevalence and severity of anemia, iron deficiency and hookworm infection when made available to Vietnamese women over a 12-month period.

Density and shape as CT predictors of intracerebral hemorrhage growth.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) growth predicts mortality and functional outcome. We hypothesized that irregular hematoma shape and density heterogeneity, reflecting active, multifocal bleeding or a variable bleeding time course, would predict ICH growth. METHODS: Three raters examined baseline sub-3-hour CT brain scans of 90 patients in the placebo arm of a Phase IIb trial of recombinant activated Factor VII in ICH. Each rater, blinded to growth data, independently applied novel 5-point categorical scales of density and shape to randomly presented baseline CT images of ICH. Density and shape were defined as either homogeneous/regular (Category 1 to 2) or heterogeneous/irregular (Category 3 to 5). Within- and between-rater reliability was determined for these scales. Growth was assessed as a continuous variable and using 3 binary definitions: (1) any ICH growth; (2) >or=33% or >or=12.5 mL ICH growth; and (3) radial growth >1 mm between baseline and 24-hour CT scan. Patients were divided into tertiles of baseline ICH volume: "small" (0 to 10 mL), "medium" (10 to 25 mL), and "large" (25 to 106 mL). RESULTS: Inter- and intrarater agreements for the novel scales exceeded 85% (+/-1 category). Median growth was significantly higher in the large-volume group compared with the small group (P<0.001) and in heterogeneous compared with homogeneous ICH (P=0.008). Median growth trended higher in irregular ICHs compared with regular ICHs (P=0.084). Small ICHs were more regularly shaped (43%) than medium (17%) and large (3%) ICHs (P<0.001). Small ICHs were more homogeneous (73%) compared with medium (37%) and large (17%) ICHs (P<0.001). Adjusting for baseline ICH volume and time to scan, density heterogeneity, but not shape irregularity, independently predicted ICH growth (P=0.046) on a continuous growth scale. CONCLUSIONS: Large ICHs were significantly more irregular in shape, heterogeneous in density, and had greater growth. Density heterogeneity independently predicted ICH growth using some definitions.

A pilot study of resistance to aspirin in stroke patients.

Aspirin resistance has been shown to be a significant risk factor for recurrent cardiovascular ischaemic events. However, there are a lack of data correlating aspirin resistance and risk of cerebrovascular ischaemic events. This pilot study aimed to determine the prevalence of aspirin resistance in an Australian stroke population and to correlate aspirin resistance with an increased risk of ischaemic stroke. Fifty patients treated with aspirin for 2 years were tested for aspirin resistance using the Ultegra Rapid Platelet Function Assay (Accumetrics, San Diego, CA, USA) on admission to Royal Melbourne Hospital for ischaemic stroke. The 2-year history of ischaemic stroke and transient ischaemic attack (TIA) were assessed. Prevalence of aspirin resistance among our patients was 30%. Univariate analysis suggested a non-significant trend towards increased rate of previous ischaemic stroke or TIA and aspirin resistance (odds ratio, OR=3.88; 95% confidence interval 0.54-29.87; p=0.18). This study shows that aspirin resistance is prevalent within the Australian ischaemic stroke population.

Improving antibiotic prescribing for adults with community acquired pneumonia: Does a computerised decision support system achieve more than academic detailing alone?--A time series analysis.

BACKGROUND: The ideal method to encourage uptake of clinical guidelines in hospitals is not known. Several strategies have been suggested. This study evaluates the impact of academic detailing and a computerised decision support system (CDSS) on clinicians' prescribing behaviour for patients with community acquired pneumonia (CAP). METHODS: The management of all patients presenting to the emergency department over three successive time periods was evaluated; the baseline, academic detailing and CDSS periods. The rate of empiric antibiotic prescribing that was concordant with recommendations was studied over time comparing pre and post periods and using an interrupted time series analysis. RESULTS: The odds ratio for concordant therapy in the academic detailing period, after adjustment for age, illness severity and suspicion of aspiration, compared with the baseline period was OR = 2.79 [1.88, 4.14], p < 0.01, and for the computerised decision support period compared to the academic detailing period was OR = 1.99 [1.07, 3.69], p = 0.02. During the first months of the computerised decision support period an improvement in the appropriateness of antibiotic prescribing was demonstrated, which was greater than that expected to have occurred with time and academic detailing alone, based on predictions from a binary logistic model. CONCLUSION: Deployment of a computerised decision support system was associated with an early improvement in antibiotic prescribing practices which was greater than the changes seen with academic detailing. The sustainability of this intervention requires further evaluation.

Anemia, iron deficiency, meat consumption, and hookworm infection in women of reproductive age in northwest Vietnam.

Iron deficiency anemia poses an important public health problem for women of reproductive age living in developing countries. We assessed the prevalence of iron deficiency and anemia and associated risk factors in a community-based sample of women living in a rural province of northwest Vietnam. A cross-sectional survey, comprised of written questionnaires and laboratory analysis of hemoglobin (Hb), ferritin, transferrin receptor, and stool hookworm egg count, was undertaken, and the soluble transferrin receptor/log ferritin index was calculated. Of 349 non-pregnant women, 37.53% were anemic (Hb < 12 g/dL), and 23.10% were iron deficient (ferritin < 15 ng/L). Hookworm infection was present in 78.15% of women, although heavy infection was uncommon (6.29%). Iron deficiency was more prevalent in anemic than non-anemic women (38.21% versus 14.08%, P < 0.001). Consumption of meat at least three times a week was more common in non-anemic women (51.15% versus 66.67%, P = 0.042). Mean ferritin was lower in anemic women (18.99 versus 35.66 ng/mL, P < 0.001). There was no evidence of a difference in prevalence (15.20% versus 17.23%, P = 0.629) or intensity (171.07 versus 129.93 eggs/g, P = 0.412) of hookworm infection between anemic and non-anemic women. Although intensity of hookworm infection and meat consumption were associated with indices of iron deficiency in a multiple regression model, their relationship with hemoglobin was not significant. Anemia, iron deficiency, and hookworm infection were prevalent in this population. Intake of meat was more clearly associated with hemoglobin and iron indices than hookworm. An approach to addressing iron deficiency in this population should emphasize both iron supplementation and deworming.

Vitamin D deficiency is associated with tuberculosis and latent tuberculosis infection in immigrants from sub-Saharan Africa.

Among African immigrants in Melbourne, Victoria, Australia, we demonstrated lower geometric mean vitamin D levels in immigrants with latent tuberculosis infection than in those with no Mycobacterium tuberculosis infection (P=.007); such levels were also lower in immigrants with tuberculosis or past tuberculosis than in those with latent tuberculosis infection (P=.001). Higher vitamin D levels were associated with lower probability of any M. tuberculosis infection (P=.001) and lower probability of tuberculosis or past tuberculosis (compared with latent tuberculosis infection; P=.001).

The improvement in survival of expanded criteria donor kidneys with transplantation era.

BACKGROUND: To compensate for the shortage of donor kidneys, use of expanded donor criteria (ECD) has been adopted by many transplant centres. Multiple criteria on which to score such kidneys have been proposed but the evidence base for the definitions is derived from retrospective and registry data only. We aimed to see if analysis of ECD in our population would indicate the need to change our donor selection process. METHODS: Data on primary kidney transplants (minimum follow-up two yr) from 1989 to 2004 were reviewed (n = 635). The primary study endpoint was overall graft survival. Published ECD, including the United Network for Organ Sharing (UNOS) ECD criteria were assessed as potential prognostic variables, in a multivariable Cox proportional hazards model. RESULTS: Patients transplanted after 1996 had improved graft survival compared to those transplanted pre-1996 HR = 0.51 (0.35-0.76), p = 0.0001. Pre-1996 UNOS defined ECD kidneys had a markedly increased risk of graft failure compared to live donor kidneys HR = 3.52 (1.9-6.35), p < 0.001. Post-1996 ECD kidneys had similar prognosis compared to live donor kidneys HR 0.38 (0.1-1.59), p = 0.184. The observed improvement in graft survival was not explained by changes in donor source, cause of end stage renal failure (ESRF), human leukocyte antigen mismatch, recipient age or any histological parameter on implantation biopsy. CONCLUSIONS: The explanation for improved overall graft survival and marked improved survival of ECD kidneys is unclear, but introduction of mycophenolate and subsequent falls in calcineurin inhibitor doses over the study period could be potential factors. These results provide some justification for our current selection and management of ECD kidneys.

Identifying severe community-acquired pneumonia in the emergency department: a simple clinical prediction tool.

OBJECTIVE: To identify independent predictors of severe pneumonia in a local population, and create a simple severity score that would be useful in the ED. METHODS: Data on the clinical features of patients presenting to hospital with community-acquired pneumonia were collected. Multivariate logistic regression was used to identify independent predictors of death, requirement for ventilatory or inotropic support, and these combined. These predictors were used to modify an existing severity score, and its performance was tested in a second cohort of patients. RESULTS: A total of 392 patients in the derivation, and 330 in the validation cohorts. Independent predictors of 'death and/or requirement for ventilatory or inotropic support' were: systolic blood pressure (BP) <90 mmHg (OR 3.49 [95% CI 1.12-10.38]); acute confusion (OR 5.48 [95% CI 2.74-10.99]); oxygen saturations < or =90% (OR 3.49 [95% CI 1.77-6.89]); and respiratory rate > or =30/min (OR 2.65 [95% CI 1.35-5.21]). Age >65 years was not an independent predictor in this patient group (OR 0.52 [95% CI 0.23-1.16]). This information was used to propose that severe pneumonia could be predicted by two or more of: acute confusion; oxygen saturations < or =90%; respiratory rate > or =30/min; and either systolic BP <90 mmHg; or diastolic BP < or =60 mmHg. In a separate cohort, the performance of this score was similar to other tools. CONCLUSION: This provides a practical tool that can be used to 'flag' impending patient demise. Its advantages are that it is simple, uses predictive variables, does not require invasive testing, and removes bias regarding patient age. Like other tools, its accuracy is not perfect, and it should only be used to augment clinical judgement.

CT coronary angiography predicts the outcome of percutaneous coronary intervention of chronic total occlusion.

BACKGROUND: The success rate of percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) is relatively low. Further evaluation of CTO lesion with CT coronary angiography (CT-CA) may help to better select patients that would benefit from percutaneous revascularization. We aimed to test the possible association between failed PCI and transluminal calcification of CTO as assessed by CT-CA. METHODS: Patients with CTO awaiting PCI were scanned with a 16-slice CT. A cardiologist and a radiologist assessed transluminal calcification of CTO lesions on CT images while an interventional cardiologist at a core laboratory assessed conventional variables of invasive fluoroscopic coronary angiography (FCA) associated with failed PCI of CTO. The significance of CT and FCA variables in association with failed PCI were analyzed. RESULTS: In a cohort of 39 patients with 43 CTO lesions, 24 lesions were successfully revascularized. Transluminal calcification > or =50% as assessed on CT-CA was strongly associated with failed PCI (odds ratio [OR] of PCI success = 0.10, 95% confidence interval [CI]: 0.02-0.47, P = 0.003). Blunt stump as seen on FCA was also associated with failed PCI (OR of PCI success = 0.24, 95% CI: 0.07-0.86, P = 0.029). There was no significant evidence to support that the duration of CTO, presence of side branch and bridging collaterals, and the absence of microchannels as assessed with FCA were associated with failed PCI. On multivariate analysis, transluminal calcification > or =50% on CT-CA was the only significant predictor of failed PCI. CONCLUSIONS: Heavy transluminal calcification as assessed with CT-CA is an independent predictor of failed PCI of CTO. CT-CA may have a role in the work-up of CTO patients prior to PCI.

'MRI-negative PET-positive' temporal lobe epilepsy (TLE) and mesial TLE differ with quantitative MRI and PET: a case control study.

BACKGROUND: 'MRI negative PET positive temporal lobe epilepsy' represents a substantial minority of temporal lobe epilepsy (TLE). Clinicopathological and qualitative imaging differences from mesial temporal lobe epilepsy are reported. We aimed to compare TLE with hippocampal sclerosis (HS+ve) and non lesional TLE without HS (HS-ve) on MRI, with respect to quantitative FDG-PET and MRI measures. METHODS: 30 consecutive HS-ve patients with well-lateralised EEG were compared with 30 age- and sex-matched HS+ve patients with well-lateralised EEG. Cerebral, cortical lobar and hippocampal volumetric and co-registered FDG-PET metabolic analyses were performed. RESULTS: There was no difference in whole brain, cerebral or cerebral cortical volumes. Both groups showed marginally smaller cerebral volumes ipsilateral to epileptogenic side (HS-ve 0.99, p = 0.02, HS+ve 0.98, p < 0.001). In HS+ve, the ratio of epileptogenic cerebrum to whole brain volume was less (p = 0.02); the ratio of epileptogenic cerebral cortex to whole brain in the HS+ve group approached significance (p = 0.06). Relative volume deficits were seen in HS+ve in insular and temporal lobes. Both groups showed marked ipsilateral hypometabolism (p < 0.001), most marked in temporal cortex. Mean hypointensity was more marked in epileptogenic-to-contralateral hippocampus in HS+ve (ratio: 0.86 vs 0.95, p < 0.001). The mean FDG-PET ratio of ipsilateral to contralateral cerebral cortex however was low in both groups (ratio: HS-ve 0.97, p < 0.0001; HS+ve 0.98, p = 0.003), and more marked in HS-ve across all lobes except insula. CONCLUSION: Overall, HS+ve patients showed more hippocampal, but also marginally more ipsilateral cerebral and cerebrocortical atrophy, greater ipsilateral hippocampal hypometabolism but similar ipsilateral cerebral cortical hypometabolism, confirming structural and functional differences between these groups.

Predictors of early cardiac morbidity and mortality after ischemic stroke.

BACKGROUND AND PURPOSE: In the first 3 months after acute ischemic stroke, 2% to 6% of patients die from cardiac causes. This may reflect preexisting cardiac disease, cardiac dysfunction related to the acute neurohumoral and autonomic stress response to stroke, or both. Delineation of a high-risk group could facilitate prevention strategies. We aimed to describe the temporal profile of cardiac risk after stroke and develop a predictive model of serious cardiac adverse events (SCAEs) using baseline variables. METHODS: We used data from the one trial in the Virtual International Stroke Trials Archive that matched prespecified criteria. Survival analysis was used to describe the temporal profile of cardiac events after stroke. Prognostic determinants were assessed with multivariable logistic regression, and a risk score was derived from the key predictor variables. RESULTS: Of 846 ischemic stroke patients, 35 (4.1%) died from cardiac causes and 161 (19.0%) suffered at least one SCAE. The hazard of cardiac death was highest (0.001/d) in the second week. Hazard of a first SCAE peaked at 0.02/d between day 2 and 3. The 5 factors most predictive of SCAEs were a history of heart failure (OR 3.33 [2.28, 4.89], P<0.001), diabetes (OR 2.11 [1.39, 3.21], P<0.001), baseline creatinine >115 micromol/L (OR 1.77 [1.16, 2.70], P=0.008), severe stroke (OR 1.98 [1.34,2.91], P=0.001), and a long QTc or ventricular extrasystoles on ECG (OR 1.93 [1.31, 2.85], P=0.001). Risk of SCAEs ranged from 6.3% (no predictors) to 62.2% (> or =4 predictors). CONCLUSIONS: Serious cardiac events are common in the acute period after stroke. Patients at highest risk are identifiable and may benefit from more aggressive strategies to improve survival.

Practicality, safety and accuracy of computed tomography coronary angiography in the evaluation of low TIMI-risk score chest pain patients: a pilot study.

OBJECTIVES: The present pilot study aimed to assess the practicality, safety and accuracy of performing CT coronary angiography (CT-CA) in the evaluation of acute chest pain of patients with low thrombolysis in myocardial infarction (TIMI) risk scores. METHODS: The present prospective observational study was undertaken in a university teaching hospital between November 2004 and December 2005. Participants were a convenience sample of patients admitted to hospital for investigation of chest pain with TIMI risk scores <3. Consenting patients underwent CT-CA within 48 h of presentation. Outcomes of interest were practicality (proportion of diagnostic quality scans obtained and preparation time for CT-CA), rate of serious adverse events, and accuracy at the patient level using selective coronary angiography as the reference standard. RESULTS: Thirty-four patients were recruited. Diagnostic quality scans were obtained in 26/34 or 76% of patients (four failed CT-CA and four non-diagnostic scans). The median CT preparation time was 1.9 h (range 0.17-4.0). No serious adverse events were found. Fourteen of those 26 patients with diagnostic CT-CA subsequently had selective coronary angiography, of which nine were positive. The sensitivity and specificity of CT-CA in identifying patients with significant coronary artery disease were 9/9 (100%; 95% confidence interval 72-100%) and 4/5 (80%; 95% confidence interval 28-100%), respectively. CONCLUSIONS: The majority of acute chest pain patients with low TIMI risk scores were successfully scanned with a 16-slice CT to produce CT-CA studies with good diagnostic quality and accuracy. No major adverse events were found. The place of CT-CA in diagnostic workup for chest pain remains to be defined.

Frequency and temporal profile of poststroke hyperglycemia using continuous glucose monitoring.

OBJECTIVE: Poststroke hyperglycemia (PSH) is common and has adverse effects on outcome. In this observational study, we aimed to describe the frequency and temporal profile of PSH using a continuous glucose monitoring system (CGMS) in patients with and without diabetes. RESEARCH DESIGN AND METHODS: Fifty-nine patients with acute hemispheric ischemic stroke were prospectively studied with the CGMS, regardless of medication, admission plasma glucose value, and diabetes status. The CGMS records interstitial glucose every 5 min for 72 h. RESULTS: On admission, 36% of patients had preexisting diabetes. At the earliest analyzed time point of 8 h from stroke onset, 50% of nondiabetic subjects and 100% of diabetic patients were hyperglycemic (> or =7 mmol/l). This early-phase hyperglycemia was followed by a decrease in glucose 14-16 h poststroke when only 11% of nondiabetic and 27% of diabetic patients were hyperglycemic. A late hyperglycemic phase 48-88 h poststroke was observed in 27% of nondiabetic and 78% of diabetic patients. Thirty-four percent of nondiabetic and 86% of diabetic patients were hyperglycemic for at least a quarter of the monitoring period. Multivariate regression analysis demonstrated that diabetes, insular cortical ischemia, and increasing age independently predicted higher glucose values. CONCLUSIONS: Poststroke hyperglycemia is common and prolonged despite treatment based on current guidelines. There are early and late hyperglycemic phases in nondiabetic as well as diabetic patients. Treatment protocols with frequent glucose measurement and intensive glucose-lowering therapy for a minimum of 72 h poststroke need to be evaluated.

Reduction of broad-spectrum antibiotic use with computerized decision support in an intensive care unit.

OBJECTIVE: To implement and evaluate the effect of a computerized decision support tool on antibiotic use in an intensive care unit (ICU). DESIGN: Prospective before-and-after cohort study. SETTING: Twenty-four bed tertiary hospital adult medical/surgical ICU. PARTICIPANTS: All consecutive patients from May 2001 to November 2001 (N = 524) and March 2002 to September 2002 (N = 536). INTERVENTION: A real-time microbiology browser and computerized decision support system for isolate directed antibiotic prescription. MAIN OUTCOME MEASURES: Number of courses of antibiotic prescribed, antibiotic utilization (defined daily doses (DDDs)/100 ICU bed-days), antibiotic susceptibility mismatches, and system uptake. RESULTS: There was a significant reduction in the proportion of patients prescribed carbapenems [odds ratio (OR) = 0.61, 95% confidence interval (CI) = 0.39-0.97, P = 0.04], third-generation cephalosporins (OR = 0.58, 95% CI = 0.42-0.79, P = 0.001), and vancomycin (OR = 0.67, 95% CI = 0.45-1.00, P = 0.05) after adjustment for risk factors including Apache II score, suspected infection, positive microbiology, intubation, and length of stay. The decision support tool was associated with a 10.5% reduction in both total antibiotic utilization (166-149 DDDs/100 ICU bed days) and the highest volume broad-spectrum antibiotics. There were fewer susceptibility mismatches for initial antibiotic therapy (OR = 0.63, 95% CI = 0.39-0.98, P = 0.02) and increased de-escalation to narrower spectrum antibiotics. Uptake of the program was high with 6028 access episodes during the 6-month evaluation period. CONCLUSIONS: This tool streamlined collation and clinical use of microbiology results and integrated into the daily ICU workflow. Its introduction was accompanied by a reduction in both total and broad-spectrum antibiotic use and an increase in the number of switches to narrower spectrum antibiotics.

Double-blind, placebo-controlled study on the effect of the aldosterone receptor antagonist spironolactone in patients who have persistent proteinuria and are on long-term angiotensin-converting enzyme inhibitor therapy, with or without an angiotensin II receptor blocker.

Studies have shown that dual therapy with angiotensin-converting enzyme inhibitors (ACEI) and either angiotensin II receptor blockers or aldosterone receptor antagonists is more effective in reducing proteinuria than either agent used alone. The questions that remain are as follows: (1) Which of these agents should be used as dual therapy with the ACEI? (2) Does a higher level of blockade of the renin-angiotensin-aldosterone system with triple therapy offer an advantage over dual blockade? A 3-mo randomized, double-blind, placebo-controlled study was performed in 41 patients with proteinuria >1.5 g/d. Four treatment groups were compared: (1) Ramipril + spironolactone placebo + irbesartan placebo, (2) ramipril + irbesartan + spironolactone placebo, (3) ramipril + irbesartan placebo + spironolactone, and (4) ramipril + irbesartan + spironolactone. The percentage change in protein excretion differed according to treatment arm (ANOVA: F(3,35) = 8.6, P < 0.001). Pair-wise comparison showed that greater reduction in protein excretion occurred in treatment regimens that incorporated spironolactone. The reduction in proteinuria at 3 mo was as follows: Group 1, 1.4%; group 2, 15.7%; group 3, 42.0%; and group 4, 48.2%. The reduction in proteinuria among patients who were taking spironolactone-containing regimens was sustained at 6 and 12 mo. This study suggests that aldosterone receptor blockade offers a valuable adjuvant treatment when used with ACEI therapy for the reduction of proteinuria. Results suggest no advantage of triple blockade over dual blockade of the renin-angiotensin-aldosterone system to reduce proteinuria.