Prophylactic acid suppressants in patients with primary neurologic injury: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Neurocritical care patients are at risk of stress-induced gastrointestinal ulceration. We performed a systematic review and meta-analysis of stress ulcer prophylaxis (SUP) in critically ill adults admitted with a primary neurologic injury. MATERIALS AND METHODS: We included randomized controlled trials (RCTs) comparing SUP with histamine-2-receptor antagonists (H2RAs) or proton pump inhibitors (PPIs) to placebo/no prophylaxis, as well as to each other. The primary outcome was in-ICU gastrointestinal bleeding (GIB). Predefined secondary outcomes were all-cause 30-day mortality, ICU length of stay (LOS), nosocomial pneumonia, and other complications. RESULTS: We identified 14 relevant trials enrolling 1036 neurocritical care patients; 11 trials enrolling 930 patients were included in the meta-analysis. H2RAs resulted in a lower incidence of GIB as compared to placebo or no prophylaxis (Risk ratio [RR] 0.42, 95% CI 0.30-0.58; p < 0.001); PPIs with a lower risk of GIB compared to placebo/no prophylaxis (RR 0.37, 95% CI 0.23-0.59; p < 0.001). No significant difference was observed in GIB comparing PPIs with H2RAs (RR 0.53, 95% CI 0.26-1.06; p = 0.07; I2 = 0%). CONCLUSIONS: In neurocritical care patients, the overall high or unclear risk of bias of individual trials, the low event rates, and modest sample sizes preclude strong clinical inferences about the utility of SUP.

Impact of the JUPITER trial on statin prescribing for primary prevention.

STUDY OBJECTIVE: As the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial identified a new population of individuals with cholesterol levels below traditional treatment thresholds but with elevated high-sensitivity C-reactive protein (hs-CRP) levels who may benefit from primary prevention with statin therapy, we sought to evaluate the impact of this trial on the incident prescription rates of rosuvastatin alone as well as all statins in a primary prevention population. DESIGN: Population-based, cross-sectional time-series analysis. DATA SOURCE: Administrative health care databases in Ontario, Canada. PATIENTS: A total of 299,809 incident statin users 66 years or older were identified during the study period, from January 1, 2003, to March 31, 2011, who were prescribed statin therapy for primary prevention. MEASUREMENTS AND MAIN RESULTS: We evaluated the incident rate of rosuvastatin and all statin use during each quarter of the study period. Overall, no significant trends in all incident statin use were observed (p=0.99). Furthermore, no significant differences were observed in incident rates of rosuvastatin (p=0.21) or all statin (p=0.41) use after the publication of the JUPITER trial. Despite the lack of impact of the JUPITER trial on rosuvastatin or all statin utilization, the relative market share of rosuvastatin increased from 9% to 65% over the study period. CONCLUSION: The publication of the JUPITER trial did not significantly affect trends in overall statin and rosuvastatin prescribing patterns for primary prevention in this study. Increases in the relative market share of rosuvastatin may be attributed to the impact of the pharmaceutical industry on prescribing patterns. Our results highlight the need to further improve the integration of evidence-based prescribing into cost-effective clinical practice.

Placental weight and neurologic outcome in the infant: a review.

OBJECTIVE: To review the agreement of published standards on placental weights (PW) and fetal-placental (F/P) ratios, examine factors contributing to PW and ask whether aberrant placental weight is associated with adverse neurologic outcome. METHODS: We conducted a literature search for standards of PW, F/P ratio and the relationship of PW to perinatal death, neonatal encephalopathy or cerebral palsy. We reviewed 17 studies of normative PW and 10 of F/P ratios. Since 1990, seven studies compared mean and extreme percentile bounds between 35 and 42 weeks of gestation. Nine publications examined PW and neurologic outcome. RESULTS: Untrimmed placentas were heavier by 131-193 g. F/P ratios differed by 0.2-2.34 between trimmed and untrimmed placentas. Fresh, frozen or fixed preparation prior to weighing had minimal effect on weight. Gender and race had negligible affect. Placentas from caesarean sections averaged 75 g heavier than vaginal deliveries. There were no consistent associations of aberrant PW and neurologic outcome. CONCLUSIONS: Reference standards of recent studies on trimmed placentas were largely in agreement. Current findings relating aberrant PW and adverse neurologic outcome are inconclusive. Further study of the relationship between placental weight and neonatal encephalopathy or cerebral palsy is warranted, in representative populations using within-study controls.

The role of therapeutic drug monitoring of imatinib in patients with chronic myeloid leukemia and metastatic or unresectable gastrointestinal stromal tumors.

Imatinib mesylate is a tyrosine kinase inhibitor used as first-line treatment in Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) and metastatic or unresectable gastrointestinal stromal tumors (GIST). Therapeutic drug monitoring (TDM) for imatinib has been suggested to improve efficacy, assess compliance, and evaluate drug-drug interactions. Imatinib has proven efficacy in improving treatment response and survival in patients with Ph+ CML and GIST. Several analytical methods are available to quantify total plasma imatinib concentrations. A good relationship exists between total imatinib plasma concentrations and pharmacologic response. Clinical evaluation of pharmacologic response to imatinib alone may be insufficient given the long duration of therapy before clinical response in patients with Ph+ CML and GIST. Thus, the authors have used a previously published 9-step decision-making algorithm to evaluate the utility of TDM for imatinib. The suggested trough concentrations for improved complete cytogenetic or major molecular response in patients with Ph+ CML and improved time to progression for patients with GIST are >1000 and >1100 ng/mL, respectively. Imatinib exhibits interindividual pharmacokinetic variability. Increased apparent clearance of imatinib has been observed in chronic phase chronic myeloid leukemia and increased body weight. Decreased apparent clearance has been observed in renal impairment and patients on concomitant medications with potent inhibition of cytochrome P450 3A4. Duration of therapy in patients with Ph+ CML and GIST is lifelong. Based on the available evidence, TDM for imatinib may provide additional information on efficacy, compliance, and safety than clinical evaluation alone. Patients with suboptimal response to treatment, treatment failure, rare adverse events, drug interactions, or suspected nonadherence will attain the greatest benefit from TDM.

Safety and efficacy of high-intensity focused ultrasound atop coronary arteries during epicardial catheter ablation.

BACKGROUND: Coronary arterial injury continues to be a limitation of epicardial catheter ablation using currently available energy sources. Application of high intensity focused ultrasound (HIFU) energy may avoid such injury due to its theoretical ability to focus energy beyond the ablation element and create lesions at depth. OBJECTIVE: This study evaluated the safety of HIFU applications delivered directly over the left anterior descending (LAD) artery in an open-chest swine model. METHODS: Ten swine underwent median sternotomy. A prototype HIFU probe was placed atop the LAD. Forty-three therapies along the LAD (60-seconds/6 watt) were analyzed. Three, 3, and 4 swine were studied at 2, 4, and 8 weeks and subsequently sacrificed. Lesions were scored (0-4) depending on the percent circumferential involvement of arteries. RESULTS: Lesion area increased minimally from 54.5 ± 18.0 mm(2) at 2 weeks to 56.9 ± 20.6 mm(2) at 8 weeks, and depth increased moderately from 13.2 ± 2.5 mm to 15.5 ± 3.4 mm. At 2, 4, and 8 weeks, the mean injury score of the LAD was 0.8 ± 0.3, 1.5 ± 0.9, and 2.0 ± 0.7. No/minimal arterial injury was seen in 64% of all sections. However, a progressive increase in injury resulted in 89% of all sections showing any injury at 8 weeks. One animal developed occlusion of the distal LAD. CONCLUSIONS: HIFU has the potential to create deep ventricular lesions with relative sparing of the LAD. The incremental arterial damage noted over time warrants further evaluation to support the viability of focusing ultrasound energy beyond vulnerable critical structures to ablate deeper targets.

Correlations between gene expression and mercury levels in blood of boys with and without autism.

Gene expression in blood was correlated with mercury levels in blood of 2- to 5-year-old boys with autism (AU) compared to age-matched typically developing (TD) control boys. This was done to address the possibility that the two groups might metabolize toxicants, such as mercury, differently. RNA was isolated from blood and gene expression assessed on whole genome Affymetrix Human U133 expression microarrays. Mercury levels were measured using an inductively coupled plasma mass spectrometer. Analysis of covariance (ANCOVA) was performed and partial correlations between gene expression and mercury levels were calculated, after correcting for age and batch effects. To reduce false positives, only genes shared by the ANCOVA models were analyzed. Of the 26 genes that correlated with mercury levels in both AU and TD boys, 11 were significantly different between the groups (P(Diagnosis*Mercury) ≤ 0.05). The expression of a large number of genes (n = 316) correlated with mercury levels in TD but not in AU boys (P ≤ 0.05), the most represented biological functions being cell death and cell morphology. Expression of 189 genes correlated with mercury levels in AU but not in TD boys (P ≤ 0.05), the most represented biological functions being cell morphology, amino acid metabolism, and antigen presentation. These data and those in our companion study on correlation of gene expression and lead levels show that AU and TD children display different correlations between transcript levels and low levels of mercury and lead. These findings might suggest different genetic transcriptional programs associated with mercury in AU compared to TD children.

Can bedside ultrasound assist in determining whether serum creatinine is elevated in cases of acute urinary retention?

BACKGROUND: There are no guidelines to determine which patients with acute urinary retention (AUR) require blood testing (i.e., serum creatinine) to assess for renal failure. OBJECTIVE: To determine if hydronephrosis on bedside ultrasound correlates with an abnormal serum creatinine (Cr) level in cases of AUR. METHODS: This was a prospective, observational study of subjects clinically diagnosed with AUR at two associated urban academic centers from October 2004 through August 2006. Emergency physicians completed a data form and performed a bedside ultrasound to determine the presence or absence of hydronephrosis. The data collected included suspected cause of AUR, amount of urinary output after Foley insertion, and blood test results. Follow-up was obtained by telephone and electronic medical record for 1 month. Standard statistics were employed. RESULTS: Among 96 enrolled subjects with AUR, 43 had a serum Cr level obtained on the initial visit, and 10 (23%; 95% confidence interval [CI] 11-36) of these had an elevated Cr (10% [95% CI 4-16] of the study cohort). The test characteristics of hydronephrosis on bedside ultrasound to detect elevation in Cr were a sensitivity, specificity, positive predictive value, and negative predictive value of 70%, 67%, 39%, and 88%, respectively. CONCLUSION: In cases of AUR, the prevalence of elevated creatinine is high, and hydronephrosis based on bedside ultrasonography does not correlate with elevation in creatinine.

Gynecological disorders in geriatric emergency medicine.

Emergency physicians must be competent in caring for elderly women because they constitute the fastest growing segment of the population in the United States. Familiarity with acute geriatric gynecologic issues is crucial to providing satisfactory health care for these patients with complaints relating to incontinence, pelvic floor dysfunction, and other gynecologic conditions. Vigilant suspicion for malignancy should be maintained in facilities that service patients without primary health care or insurance. This article provides a systematic approach to emergency department management of common geriatric gynecological conditions. Anatomical and physiological changes are discussed, as well as the geriatric pelvic examination, malignancy, urinary tract infection, incontinence, pelvic organ prolapse, and vulvovaginitis.